FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2605678774> ?p ?o ?g. }

• W2605678774 endingPage "561" @default.
• W2605678774 startingPage "549" @default.
• W2605678774 abstract "Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung. We propose that host interactions with microbes are critical for establishing the immune landscape of the lungs. Pulmonary immune homeostasis is maintained by a network of tissue-resident cells that continually monitor the external environment, and in health, instruct tolerance to innocuous inhaled particles while ensuring that efficient and rapid immune responses can be mounted against invading pathogens. Here we review the multiple pathways that underlie effective lung immunity in health, and discuss how these may be affected by external environmental factors and contribute to chronic inflammation during disease. In this context, we examine the current understanding of the impact of the microbiota in immune development and function and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung. We propose that host interactions with microbes are critical for establishing the immune landscape of the lungs. Maturation of the pulmonary immune system occurs in an antigen-rich postnatal environment. Initially, the adaptive immune system has limited capacity to induce memory responses and this develops gradually. Although this early life immune programming likely has implications for lifelong immune health, there is little mechanistic evidence identifying underlying molecular pathways. It is well established that multiple viral infections in early life predispose to wheezing and asthma in childhood, yet certain bacterial exposures are thought to be protective. In addition, patients with chronic lung diseases experience disease exacerbations that are thought to be provoked by pathogens, which might otherwise be innocuous in a healthy person. Although the lungs are thought to be sterile in utero, postnatal exposures to viruses, bacteria, and fungi contained within the inhaled or aspirated environment not only form and shape the microbiota, but are vital for the education and maturation of the pulmonary immune system. Disturbance of microbes present at mucosal surfaces by inappropriate or serial antibiotic usage also affects immune development and might cause a microbe that is normally a commensal to become pathogenic. The environment that a child grows up in also has a part to play in the education of the respiratory immune system because epidemiological studies show that premature birth, birth order, number of siblings, living with pets, living next to a major road, and parental smoking all increase the risks for developing lung disease in later life. Landmark studies showing that exposure to farmyard dust in early life is protective against development of allergies and asthma (Ege et al., 2011Ege M.J. Mayer M. Normand A.C. Genuneit J. Cookson W.O. Braun-Fahrländer C. Heederik D. Piarroux R. von Mutius E. Group G.T.S. GABRIELA Transregio 22 Study GroupExposure to environmental microorganisms and childhood asthma.N. Engl. J. Med. 2011; 364: 701-709Crossref PubMed Scopus (570) Google Scholar, von Mutius and Vercelli, 2010von Mutius E. Vercelli D. Farm living: effects on childhood asthma and allergy.Nat. Rev. Immunol. 2010; 10: 861-868Crossref PubMed Scopus (277) Google Scholar) indicate just how important our relationship with microbes is in shaping our immune systems. Experimental mouse models have underscored the importance of the pulmonary epithelium in mediating the protective effect of this farm dust (Schuijs et al., 2015Schuijs M.J. Willart M.A. Vergote K. Gras D. Deswarte K. Ege M.J. Madeira F.B. Beyaert R. van Loo G. Bracher F. et al.Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells.Science. 2015; 349: 1106-1110Crossref PubMed Scopus (100) Google Scholar). There is also evidence to show that the number and type of respiratory infections that a child encounters in early life affects pulmonary immune development and sets the trajectory for lifelong lung health. However, it is not clear that viral infections are universally bad while exposure to bacterial components is beneficial, because early colonization with Streptococcus pneumoniae, Moraxella catarrhalis, or Haemophilus influenzae is associated with an increased risk of later asthma (Bisgaard et al., 2007Bisgaard H. Hermansen M.N. Buchvald F. Loland L. Halkjaer L.B. Bønnelykke K. Brasholt M. Heltberg A. Vissing N.H. Thorsen S.V. et al.Childhood asthma after bacterial colonization of the airway in neonates.N. Engl. J. Med. 2007; 357: 1487-1495Crossref PubMed Scopus (436) Google Scholar). It is likely that the relationship between our pulmonary immune system and the microbiota is dynamic and changes with age and environmental exposures. Although respiratory diseases span the entire life course, asthma inception occurs in childhood while COPD and pulmonary fibrosis are commonly associated with older age groups. In addition, it is clear that there are significant changes in immunity associated with aging and that the elderly have an enhanced risk of pulmonary infections. Although little is known about how development of immune senescence affects pulmonary aging, it likely influences the ability to fight infections. Similarly, there is scant information regarding the healthy aging of the lung, because little investigation is carried out in healthy older people. This review examines the relationship between host immune pathways and microbial communities at the pulmonary mucosa. We highlight the vital influence of these interactions on the education and maturation of the immune system as well as their implications for the development of chronic lung diseases. Although a great deal remains to be discovered concerning the relative contribution of the local pulmonary microbiota, as compared to that of the gut or skin, in determining generation of lung immunity, a greater understanding of how the pulmonary immune system is trained or matured by encounter with bacteria, viruses, or fungi is essential to determine novel strategies for disease prevention and treatment. A complex system of local immune pathways maintain homeostasis within the lungs, and epithelial-macrophages are an integral part of this. The resident epithelial cells and airway macrophages represent a specialized unit which facilitates maintenance of the steady state but their ability to sense the ever changing inhaled environment allows for prompt reactions to potential threats. The relationship between these local defense mechanisms and the microbiota is becoming apparent and their association is dynamic across the life course. However, disturbances in the relationship have consequences for development of efficient immunity. The pulmonary epithelium provides a barrier between the outside environment and the internal tissues and provides vital first line host defense against noxious stimuli and pathogenic insults. Within the epithelium, ciliated columnar, mucus secreting goblet cells, tuft cells, and Club cells that secrete surfactant, adhere together to form a regulated, impermeable barrier due to the formation of tight junctions localized at the apical surface. Another protective feature of the airway epithelial layer is mucociliary action, which expedites clearance of particulate matter by scavenging and trapping particles and facilitates their removal by coughing. Mucus is produced at low levels in healthy airways and forms a protective layer that is vital for host defense but also for maintenance of immune homeostasis (Radicioni et al., 2016Radicioni G. Cao R. Carpenter J. Ford A.A. Wang T.T. Li Y. Kesimer M. The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome.Mucosal Immunol. 2016; 9: 1442-1454Crossref PubMed Scopus (1) Google Scholar). In particular, defects in production of Muc5B are associated with severe respiratory illness (Roy et al., 2014Roy M.G. Livraghi-Butrico A. Fletcher A.A. McElwee M.M. Evans S.E. Boerner R.M. Alexander S.N. Bellinghausen L.K. Song A.S. Petrova Y.M. et al.Muc5b is required for airway defence.Nature. 2014; 505: 412-416Crossref PubMed Scopus (143) Google Scholar). Respiratory viruses, air pollutants, and proteolytically active allergens that overcome the mucociliary barrier all have the capacity to damage the epithelium, disrupting tight junctions and increasing epithelial permeability. In addition to this barrier function, the pulmonary epithelium is immunologically active and is pivotal in the regulation of immune responses in the lung (Iwasaki et al., 2017Iwasaki A. Foxman E.F. Molony R.D. Early local immune defences in the respiratory tract.Nat. Rev. Immunol. 2017; 17: 7-20Crossref PubMed Scopus (0) Google Scholar). Pulmonary epithelial cells are able to secrete a wide range of cytokines and chemokines, as well as being in intimate contact with cells of the immune system. Expression of cell surface receptors enable them to sense and react to environmental change. Lung epithelial cells express pattern-recognition receptors (PRR), such as the Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPS) from viruses, bacteria, fungi, protozoa, and multicellular parasites (Lambrecht and Hammad, 2012Lambrecht B.N. Hammad H. The airway epithelium in asthma.Nat. Med. 2012; 18: 684-692Crossref PubMed Scopus (329) Google Scholar). In addition they can react to stress and can secrete a range of anti-microbial mediators including lysozyme, defensins, collectins, and complement components (Iwasaki et al., 2017Iwasaki A. Foxman E.F. Molony R.D. Early local immune defences in the respiratory tract.Nat. Rev. Immunol. 2017; 17: 7-20Crossref PubMed Scopus (0) Google Scholar). Many of the molecules secreted by epithelial cells in response to danger have the ability to regulate immune reactions and recruit cells of the innate and adaptive immune system. Airway epithelial cells can also contribute to the local clearance of apoptotic cells, via apoptosis and secretion of anti-inflammatory cytokines (Juncadella et al., 2013Juncadella I.J. Kadl A. Sharma A.K. Shim Y.M. Hochreiter-Hufford A. Borish L. Ravichandran K.S. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation.Nature. 2013; 493: 547-551Crossref PubMed Scopus (96) Google Scholar). This function was dependent on intracellular signaling via the small GTPase Rac1. Specific deletion of Rac1 in bronchial epithelial cells led to enhanced inflammation following allergen exposure, with decreased secretion of IL-10 but increased expression of classical type 2 cytokines IL-4, IL-5, and IL-13. Specific deletion of epithelial Rac1 also led to an increased expression of IL-33 in epithelial cells and release into the lumen after allergen exposure. Direct administration of IL-10 to the airways was able to ameliorate this enhanced type 2 inflammation. These data identify how epithelial cells might regulate allergic inflammation via expression of Rac1, which controls the balance between IL-10 and IL-33. Therefore, the initiation and maintenance of inflammation at epithelial surfaces is induced by local mechanisms that have marked effects on the outcome of the immune response. In health, the lungs are populated with a number of different macrophage populations, which display remarkable heterogeneity due to variations in origin and tissue residency, as well as environmental influences (Yona et al., 2013Yona S. Kim K.W. Wolf Y. Mildner A. Varol D. Breker M. Strauss-Ayali D. Viukov S. Guilliams M. Misharin A. et al.Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis.Immunity. 2013; 38: 79-91Abstract Full Text Full Text PDF PubMed Scopus (628) Google Scholar, Hashimoto et al., 2013Hashimoto D. Chow A. Noizat C. Teo P. Beasley M.B. Leboeuf M. Becker C.D. See P. Price J. Lucas D. et al.Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes.Immunity. 2013; 38: 792-804Abstract Full Text Full Text PDF PubMed Scopus (528) Google Scholar, Guilliams et al., 2013Guilliams M. De Kleer I. Henri S. Post S. Vanhoutte L. De Prijck S. Deswarte K. Malissen B. Hammad H. Lambrecht B.N. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF.J. Exp. Med. 2013; 210: 1977-1992Crossref PubMed Scopus (221) Google Scholar). Those macrophages resident within the airway lumen (airway macrophages, AM) are long-lived cells derived from embryonic progenitors that colonize the airways soon after birth and self renew under homeostatic conditions. AMs are distinguished from tissue dwelling interstitial macrophages (IM) via their particular repertoire of surface receptors (AM being F4/80hi, CD11c hi, SiglecFhi). Further populations of monocyte-derived macrophages are recruited to the lung during inflammatory conditions, but airway macrophages represent a first line of defense of the airways and maintain pulmonary immune homeostasis via their close interaction with other lung-resident cells, primarily pulmonary epithelial cells. Their broad program of surface receptors enables them to sense the environment and signal to local stromal cells in order to maintain immune homeostasis within the respiratory tract, but also to sense change within the inhaled environment. These signals can either be activating (TLR 2, 4, 6; IL-1R, IFNγR, and TNFR) or suppressive (CD200R, SIRPα, mannose receptor, TREM2, IL-10R, TGFβR) (Hussell and Bell, 2014Hussell T. Bell T.J. Alveolar macrophages: plasticity in a tissue-specific context.Nat. Rev. Immunol. 2014; 14: 81-93Crossref PubMed Scopus (213) Google Scholar). It is clear that close interaction and communication between airway epithelial cells and airway macrophages is vital for maintenance of immune homeostasis within the respiratory tract (Figure 1). A subset of airway macrophages communicate with epithelial cells via synchronized waves of calcium through connexion channels, which are activated via Akt to exert suppressive signals (Westphalen et al., 2014Westphalen K. Gusarova G.A. Islam M.N. Subramanian M. Cohen T.S. Prince A.S. Bhattacharya J. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity.Nature. 2014; 506: 503-506Crossref PubMed Scopus (0) Google Scholar). Interruption of this close association led to stronger responses to inhaled LPS, with increased recruitment of neutrophils and secretion of pro-inflammatory cytokines. This local pulmonary environment is critical for providing phenotypic cues for the airway macrophages: pulmonary transplantation of bone-marrow-derived macrophages led to their transformation into an AM phenotype (Suzuki et al., 2014Suzuki T. Arumugam P. Sakagami T. Lachmann N. Chalk C. Sallese A. Abe S. Trapnell C. Carey B. Moritz T. et al.Pulmonary macrophage transplantation therapy.Nature. 2014; 514: 450-454Crossref PubMed Scopus (75) Google Scholar). Similarly, while macrophages from the yolk sac or fetal liver are able to recolonize the empty pulmonary niche and develop into functional tissue resident AM, mature AM from other tissue sites were not (van de Laar et al., 2016van de Laar L. Saelens W. De Prijck S. Martens L. Scott C.L. Van Isterdael G. Hoffmann E. Beyaert R. Saeys Y. Lambrecht B.N. Guilliams M. Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages.Immunity. 2016; 44: 755-768Abstract Full Text Full Text PDF PubMed Google Scholar), illustrating the importance of the local environment. Epithelial cells and AM also cooperate to facilitate clearance of cellular debris and particulate matter. Recent evidence indicates that macrophages are able to signal to epithelial cells to fine tune phagocytosis. Secretion of insulin-like growth factor (IGF1) from macrophages occurs following exposure to inflammatory cytokines or during phagocytosis of apoptotic cells. Binding of IGF1 to its receptor expressed on non-professional antigen-presenting cells, such as local epithelial cells, temporarily redirects their phagocytic capacity such that engulfment of apoptotic cells is reduced while uptake of microparticles is increased (Han et al., 2016Han C.Z. Juncadella I.J. Kinchen J.M. Buckley M.W. Klibanov A.L. Dryden K. Onengut-Gumuscu S. Erdbrügger U. Turner S.D. Shim Y.M. et al.Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation.Nature. 2016; 539: 570-574Crossref PubMed Google Scholar). Disruption of IGF1 signaling by deletion of the IGF receptor in the epithelium enhances allergic airway inflammation and highlights the role of the airway macrophage in modulating epithelial functions. Although epithelial macrophage interactions facilitate first line defense of the airways; if appropriate a second tier of immune responses coordinated by local, tissue-resident lymphoid cells is elicited. This will then control the initiation of effector responses that mediate repair and resolution, and ultimately restitution of homeostasis. Lymphocytes circulate through the lung via the lymph, patrolling for potential antigen encounter. Specialized subsets of T cells are recruited to the lung following encounter with antigen. For example, the chemokine receptors CCR4 and CCR8 promote migration of antigen-specific Th2 cells to the lung (Cho et al., 2016Cho J.L. Ling M.F. Adams D.C. Faustino L. Islam S.A. Afshar R. Griffith J.W. Harris R.S. Ng A. Radicioni G. et al.Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation.Sci. Transl. Med. 2016; 8: 359ra132Crossref PubMed Scopus (1) Google Scholar, Lloyd et al., 2000Lloyd C.M. Delaney T. Nguyen T. Tian J. Martinez-A C. Coyle A.J. Gutierrez-Ramos J.C. CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo.J. Exp. Med. 2000; 191: 265-274Crossref PubMed Scopus (0) Google Scholar); however, the signals that mediate recruitment of specialized effector and memory cells, and crucially, those that facilitate their retention within the tissue have only recently been addressed. It is now clear that the lung harbors resident populations of both memory T cells and innate lymphoid cells, as well as other resident cells such as regulatory T cells and γδT cells—all working collaboratively with the local dendritic cell network, thereby ensuring efficient triggering of both innate and memory responses. It is clear that a subset of memory T cells remain in the lung following initial encounter with antigen and that these resident memory T cells (Trm cells) are sufficient to generate local inflammation, even in the absence of central memory T cells from secondary lymphoid organs (Park and Kupper, 2015Park C.O. Kupper T.S. The emerging role of resident memory T cells in protective immunity and inflammatory disease.Nat. Med. 2015; 21: 688-697Crossref PubMed Scopus (93) Google Scholar). CD4+ and CD8+ Trm are present even in healthy lungs, expressing CD69 and a diverse TCR repertoire (Purwar et al., 2011Purwar R. Campbell J. Murphy G. Richards W.G. Clark R.A. Kupper T.S. Resident memory T cells (T(RM)) are abundant in human lung: diversity, function, and antigen specificity.PLoS ONE. 2011; 6: e16245Crossref PubMed Scopus (108) Google Scholar, Sathaliyawala et al., 2013Sathaliyawala T. Kubota M. Yudanin N. Turner D. Camp P. Thome J.J. Bickham K.L. Lerner H. Goldstein M. Sykes M. et al.Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets.Immunity. 2013; 38: 187-197Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar). Trm form an important component of immunity at barrier surfaces and provide rapid protective immune responses during secondary infections with respiratory viruses such as influenza or RSV. Indeed, in a human RSV challenge study, higher airway CD8+ Trm correlated with reduced disease severity (Jozwik et al., 2015Jozwik A. Habibi M.S. Paras A. Zhu J. Guvenel A. Dhariwal J. Almond M. Wong E.H. Sykes A. Maybeno M. et al.RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection.Nat. Commun. 2015; 6: 10224Crossref PubMed Scopus (0) Google Scholar). The fact that Trm cells are able to facilitate the elimination of pathogenic virus even in the absence of antibody can be exploited for the generation of more effective vaccines (Jiang et al., 2012Jiang X. Clark R.A. Liu L. Wagers A.J. Fuhlbrigge R.C. Kupper T.S. Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity.Nature. 2012; 483: 227-231Crossref PubMed Scopus (263) Google Scholar). Resident memory cells might also influence immune responses to inhaled allergens. Following influenza infection of mice CD8+ memory cells in the lung can be reactivated in an antigen independent manner by cytokines such as IL-18, which led to their release of cytokines e.g., IFN-γ, that counterregulate subsequent Th2 responses, thereby protecting the mice against allergic airway inflammation (Marsland et al., 2004Marsland B.J. Harris N.L. Camberis M. Kopf M. Hook S.M. Le Gros G. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells.Proc. Natl. Acad. Sci. USA. 2004; 101: 6116-6121Crossref PubMed Scopus (0) Google Scholar). Similarly, allergen-specific Type2 memory cells persist in the murine lung after exposure to house dust mite (Hondowicz et al., 2016Hondowicz B.D. An D. Schenkel J.M. Kim K.S. Steach H.R. Krishnamurty A.T. Keitany G.J. Garza E.N. Fraser K.A. Moon J.J. et al.Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.Immunity. 2016; 44: 155-166Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). Locally derived, CD25-mediated IL2 signaling provides a comprehensive repertoire of migrational signals, including chemokine receptors that result in the generation and maintenance of these antigen-specific tissue resident T cells that can drive pathology on antigen re-encounter (Hondowicz et al., 2016Hondowicz B.D. An D. Schenkel J.M. Kim K.S. Steach H.R. Krishnamurty A.T. Keitany G.J. Garza E.N. Fraser K.A. Moon J.J. et al.Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.Immunity. 2016; 44: 155-166Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). The innate lymphoid cell family constitutes several phenotypically distinct groups of cells that lack the usual lineage markers that define classical lymphocytes, notably antigen-specific receptors and do not mediate antigen-specific responses (Diefenbach et al., 2014Diefenbach A. Colonna M. Koyasu S. Development, differentiation, and diversity of innate lymphoid cells.Immunity. 2014; 41: 354-365Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar). Although they are distributed throughout both lymphoid and non-lymphoid organs their numbers are enhanced at barrier surfaces and they are thought to be vital for maintenance of homeostasis, regulation of immunity and tissue repair (Tait Wojno and Artis, 2016Tait Wojno E.D. Artis D. Emerging concepts and future challenges in innate lymphoid cell biology.J. Exp. Med. 2016; 213: 2229-2248Crossref PubMed Google Scholar). Like effector T cells, ILCs have been classified according to the transcription factors that they express and the effector cytokines that they secrete (Spits et al., 2013Spits H. Artis D. Colonna M. Diefenbach A. Di Santo J.P. Eberl G. Koyasu S. Locksley R.M. McKenzie A.N. Mebius R.E. et al.Innate lymphoid cells--a proposal for uniform nomenclature.Nat. Rev. Immunol. 2013; 13: 145-149Crossref PubMed Scopus (827) Google Scholar). ILC2 cells are defined by the production of type2 cytokines IL-13, IL-5, and IL-4 as well as expression of the transcription factor Gata3. Indeed ectopic expression of Gata3 directs lineage negative ILCs toward an ILC2 phenotype and promotes de novo production of IL-13 and IL-5 (Klein Wolterink et al., 2013Klein Wolterink R.G. Serafini N. van Nimwegen M. Vosshenrich C.A. de Bruijn M.J. Fonseca Pereira D. Veiga Fernandes H. Hendriks R.W. Di Santo J.P. Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells.Proc. Natl. Acad. Sci. USA. 2013; 110: 10240-10245Crossref PubMed Scopus (94) Google Scholar). ILC2s direct a seemingly diverse range of in vivo functions, being involved in protective immunity during helminth infections; development of allergic inflammation, tissue repair and sustaining metabolic homeostasis (Neill et al., 2010Neill D.R. Wong S.H. Bellosi A. Flynn R.J. Daly M. Langford T.K. Bucks C. Kane C.M. Fallon P.G. Pannell R. et al.Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.Nature. 2010; 464: 1367-1370Crossref PubMed Scopus (920) Google Scholar, Diefenbach et al., 2014Diefenbach A. Colonna M. Koyasu S. Development, differentiation, and diversity of innate lymphoid cells.Immunity. 2014; 41: 354-365Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar, Tait Wojno and Artis, 2016Tait Wojno E.D. Artis D. Emerging concepts and future challenges in innate lymphoid cell biology.J. Exp. Med. 2016; 213: 2229-2248Crossref PubMed Google Scholar). ILC are thought to be tissue-resident cells. In an elegant series of experiments using mice with conjoined circulatory systems, the ILC2 found within the lung were demonstrated to be of host origin, indicating residency (Gasteiger et al., 2015Gasteiger G. Fan X. Dikiy S. Lee S.Y. Rudensky A.Y. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.Science. 2015; 350: 981-985Crossref PubMed Scopus (84) Google Scholar). Moreover, virtually all of the ILC2 and ILC1 identified were situated within the lung parenchyma rather than the circulation. Interestingly, there were few ILC3 identified within the lung, the vast majority of ILC belonging to the ILC2 subset. Long-term tissue residency was shown to be maintained locally via self-renewal during homeostatic conditions. Somewhat surprisingly, even during episodes of inflammation such as during helminth infection, expansion was largely due to local proliferation rather than recruitment. A small proportion of recruited ILC2s were observed during chronic infection phase but this only represented 10% of the total ILC population (Gasteiger et al., 2015Gasteiger G. Fan X. Dikiy S. Lee S.Y. Rudensky A.Y. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.Science. 2015; 350: 981-985Crossref PubMed Scopus (84) Google Scholar). It is notable that this was specific to the ILC2 subset since very few ILC3s were recruited and likely reflects the principal function of ILC2s in tissue repair. This might be a specific facet of the lung microenvironment since it was recently shown that ILC3 within the intestine can rapidly mobilize from cryptopatches during colitis to amplify inflammation (Pearson et al., 2016Pearson C. Thornton E.E. McKenzie B. Schaupp A.L. Huskens N. Griseri T. West N. Tung S. Seddon B.P. Uhlig H.H. Powrie F. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation.eLife. 2016; 5: e10066PubMed Google Scholar). Despite their residency in the lung, ILC2 accumulation can be facilitated by interaction with both local stromal cells as well as hematopoietic cells. Cytokines secreted by pulmonary epithelial cells such as IL-33 and TGF-β enhance the accumulation of ILC2 cells within the lung, particularly after encounter with allergen (Denney et al., 2015Denney L. Byrne A.J. Shea T.J. Buckley J.S. Pease J.E. Herledan G.M. Walker S.A. Gregory L.G. Lloyd C.M. Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function.Immunity. 2015; 43: 945-958Abstract Full Text Full Text PDF PubMed Google Scholar, Mohapatra et al., 2016Mohapatra A. Van Dyken S.J. Schneider C. Nussbaum J.C. Liang H.E. Locksley R.M. Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis.Mucosal Immunol. 2016; 9: 275-286Crossref PubMed Google Scholar). The type 2 cytokines secreted by these ILC2 are thought to contribute to the inflammatory pathology typical of allergic asthma. Alternatively, they have been shown to contribute to tissue repair during acute influenza infection via the secretion of the EGFR ligand amphiregulin. The ability of ILC to sense their local environment is thought to be a cornerstone of the local pulmonary host defense. However, the mechanisms that balance their contribution to development of lung pathology versus facilitating tissue repair are not well understood. It may be that duration of immune signals is vital because most of the in vivo mouse studies have focused on acute inflammatory models. Although ILC2 have been described as the dominant subset within the mouse lung, in the hu" @default.
• W2605678774 created "2017-04-28" @default.
• W2605678774 creator A5067602200 @default.
• W2605678774 creator A5073340353 @default.
• W2605678774 date "2017-04-01" @default.
• W2605678774 modified "2023-10-14" @default.
• W2605678774 title "Lung Homeostasis: Influence of Age, Microbes, and the Immune System" @default.
• W2605678774 cites W1442681366 @default.
• W2605678774 cites W1497519679 @default.
• W2605678774 cites W1506819190 @default.
• W2605678774 cites W1512693074 @default.
• W2605678774 cites W1547755073 @default.
• W2605678774 cites W1561788579 @default.
• W2605678774 cites W1582767991 @default.
• W2605678774 cites W1647857389 @default.
• W2605678774 cites W1945216762 @default.
• W2605678774 cites W1967879964 @default.
• W2605678774 cites W1970777915 @default.
• W2605678774 cites W1973433801 @default.
• W2605678774 cites W1977164923 @default.
• W2605678774 cites W1979637422 @default.
• W2605678774 cites W1981549976 @default.
• W2605678774 cites W1985972305 @default.
• W2605678774 cites W1989401022 @default.
• W2605678774 cites W1990121282 @default.
• W2605678774 cites W1991225939 @default.
• W2605678774 cites W1991240417 @default.
• W2605678774 cites W1991600170 @default.
• W2605678774 cites W1997396254 @default.
• W2605678774 cites W2002307060 @default.
• W2605678774 cites W2008440267 @default.
• W2605678774 cites W2008548000 @default.
• W2605678774 cites W2009101746 @default.
• W2605678774 cites W2010089859 @default.
• W2605678774 cites W2015891257 @default.
• W2605678774 cites W2018861313 @default.
• W2605678774 cites W2021604398 @default.
• W2605678774 cites W2023506796 @default.
• W2605678774 cites W2033289727 @default.
• W2605678774 cites W2034662167 @default.
• W2605678774 cites W2036564362 @default.
• W2605678774 cites W2042237784 @default.
• W2605678774 cites W2048469790 @default.
• W2605678774 cites W2049574345 @default.
• W2605678774 cites W2050591900 @default.
• W2605678774 cites W2050872483 @default.
• W2605678774 cites W2052337358 @default.
• W2605678774 cites W2054978203 @default.
• W2605678774 cites W2057192777 @default.
• W2605678774 cites W2060185417 @default.
• W2605678774 cites W2063177917 @default.
• W2605678774 cites W2065384280 @default.
• W2605678774 cites W2066168750 @default.
• W2605678774 cites W2067806364 @default.
• W2605678774 cites W2068332307 @default.
• W2605678774 cites W2072522353 @default.
• W2605678774 cites W2075951089 @default.
• W2605678774 cites W2077109336 @default.
• W2605678774 cites W2082445383 @default.
• W2605678774 cites W2082595913 @default.
• W2605678774 cites W2086914849 @default.
• W2605678774 cites W2086993280 @default.
• W2605678774 cites W2088394751 @default.
• W2605678774 cites W2089031834 @default.
• W2605678774 cites W2092520647 @default.
• W2605678774 cites W2092790181 @default.
• W2605678774 cites W2097384942 @default.
• W2605678774 cites W2099190232 @default.
• W2605678774 cites W2100646399 @default.
• W2605678774 cites W2101600300 @default.
• W2605678774 cites W2103153413 @default.
• W2605678774 cites W2105751172 @default.
• W2605678774 cites W2109561957 @default.
• W2605678774 cites W2111740348 @default.
• W2605678774 cites W2115547311 @default.
• W2605678774 cites W2116116157 @default.
• W2605678774 cites W2117502709 @default.
• W2605678774 cites W2119812316 @default.
• W2605678774 cites W2120579640 @default.
• W2605678774 cites W2120934195 @default.
• W2605678774 cites W2125178177 @default.
• W2605678774 cites W2126525177 @default.
• W2605678774 cites W2127308546 @default.
• W2605678774 cites W2127612599 @default.
• W2605678774 cites W2133756317 @default.
• W2605678774 cites W2133894777 @default.
• W2605678774 cites W2140206763 @default.
• W2605678774 cites W2141157966 @default.
• W2605678774 cites W2143631353 @default.
• W2605678774 cites W2145720531 @default.
• W2605678774 cites W2145819863 @default.
• W2605678774 cites W2147279704 @default.
• W2605678774 cites W2147516417 @default.
• W2605678774 cites W2147650681 @default.
• W2605678774 cites W2151322257 @default.
• W2605678774 cites W2152107216 @default.
• W2605678774 cites W2152174546 @default.
• W2605678774 cites W2152259491 @default.

• next