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• W2023877563 abstract "Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function in situ. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE and reveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function. Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function in situ. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE and reveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function. Skin mast cells exhibit selective uptake of IgE from the blood Selective uptake is localized to perivascular mast cells Mast cells extend cellular processes to survey vascular contents and capture IgE Mast cells are hematopoietic, tissue-resident cells that have been considered to play diverse roles in host defense and immune regulation as well as a central role in allergic disease (Galli and Tsai, 2010Galli S.J. Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.Eur. J. Immunol. 2010; 40: 1843-1851Crossref PubMed Scopus (292) Google Scholar; Gould and Sutton, 2008Gould H.J. Sutton B.J. IgE in allergy and asthma today.Nat. Rev. Immunol. 2008; 8: 205-217Crossref PubMed Scopus (836) Google Scholar; Locksley, 2010Locksley R.M. Asthma and allergic inflammation.Cell. 2010; 140: 777-783Abstract Full Text Full Text PDF PubMed Scopus (306) Google Scholar). Despite these many potential roles, recent studies, by using mouse strains with targeted mast cell deletion, have primarily served to underscore the mast cell contribution to the clinical manifestations of allergic disease (Dudeck et al., 2011Dudeck A. Dudeck J. Scholten J. Petzold A. Surianarayanan S. Köhler A. Peschke K. Vöhringer D. Waskow C. Krieg T. et al.Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens.Immunity. 2011; 34: 973-984Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar; Feyerabend et al., 2011Feyerabend T.B. Weiser A. Tietz A. Stassen M. Harris N. Kopf M. Radermacher P. Möller P. Benoist C. Mathis D. et al.Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.Immunity. 2011; 35: 832-844Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar). The mast cell contribution to allergy is largely dependent on the acquisition of monomeric immunoglobulin E (IgE) on the surface of mast cells through expression of the high affinity IgE receptor (FcεRI) (Kraft and Kinet, 2007Kraft S. Kinet J.P. New developments in FcepsilonRI regulation, function and inhibition.Nat. Rev. Immunol. 2007; 7: 365-378Crossref PubMed Scopus (452) Google Scholar). Though FcεRI can be detected on the surface of mast cell precursors (Hallgren and Gurish, 2007Hallgren J. Gurish M.F. Pathways of murine mast cell development and trafficking: tracking the roots and routes of the mast cell.Immunol. Rev. 2007; 217: 8-18Crossref PubMed Scopus (73) Google Scholar), expression of FcεRI on tissue-resident mast cells increases proportionally with serum IgE titers, suggesting the tissue as a primary site of IgE acquisition (Kraft and Kinet, 2007Kraft S. Kinet J.P. New developments in FcepsilonRI regulation, function and inhibition.Nat. Rev. Immunol. 2007; 7: 365-378Crossref PubMed Scopus (452) Google Scholar; Yamaguchi et al., 1997Yamaguchi M. Lantz C.S. Oettgen H.C. Katona I.M. Fleming T. Miyajima I. Kinet J.P. Galli S.J. IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions.J. Exp. Med. 1997; 185: 663-672Crossref PubMed Scopus (390) Google Scholar). Once mast cells are loaded with IgE, subsequent antigen binding leads to crosslinking of FcεRI molecules and the immediate release of preformed mediators, such as histamine, as well as synthesis of lipid and protein mediators (Galli and Tsai, 2010Galli S.J. Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.Eur. J. Immunol. 2010; 40: 1843-1851Crossref PubMed Scopus (292) Google Scholar). Studies of the mast cell-IgE axis have focused on the regulation of IgE production as well as the clinical manifestations of hypersensitivity responses following antigen exposure. Few studies have examined how mast cells acquire unbound IgE. Defining the mechanism by which mast cells capture IgE will fill a gap in our understanding of the mast cell-IgE axis and may provide new therapeutic approaches to severe allergic disorders. Although cell-bound IgE is found primarily in tissues, IgE production by plasma cells occurs mostly in the bone marrow, spleen, and lymph nodes (Luger et al., 2009Luger E.O. Fokuhl V. Wegmann M. Abram M. Tillack K. Achatz G. Manz R.A. Worm M. Radbruch A. Renz H. Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge.J. Allergy Clin. Immunol. 2009; 124: 819-826Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar; McMenamin et al., 1992McMenamin C. Girn B. Holt P.G. The distribution of IgE plasma cells in lymphoid and non-lymphoid tissues of high-IgE responder rats: differential localization of antigen-specific and ‘bystander’ components of the IgE response to inhaled antigen.Immunology. 1992; 77: 592-596PubMed Google Scholar; Talay et al., 2012Talay O. Yan D. Brightbill H.D. Straney E.E. Zhou M. Ladi E. Lee W.P. Egen J.G. Austin C.D. Xu M. Wu L.C. IgE+ memory B cells and plasma cells generated through a germinal-center pathway.Nat. Immunol. 2012; 13: 396-404Crossref PubMed Scopus (132) Google Scholar; Yang et al., 2012Yang Z. Sullivan B.M. Allen C.D. Fluorescent in vivo detection reveals that IgE(+) B cells are restrained by an intrinsic cell fate predisposition.Immunity. 2012; 36: 857-872Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar). Thus, the localization of IgE production is anatomically distinct from sites of IgE acquisition and effector function. As the amount of surface-bound IgE by tissue mast cells directly reflects the size of the serum IgE pool (Kraft and Kinet, 2007Kraft S. Kinet J.P. New developments in FcepsilonRI regulation, function and inhibition.Nat. Rev. Immunol. 2007; 7: 365-378Crossref PubMed Scopus (452) Google Scholar), the vasculature acts as a conduit by which unbound IgE is distributed to tissue mast cells. The vasculature also acts as a potential barrier to IgE uptake and could thereby regulate IgE delivery to tissue sites. Mast cells show a preference toward perivascular localization within tissue, wherein a majority of mast cells lie in close proximity to the basal side of the vessel wall (Galli and Tsai, 2010Galli S.J. Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.Eur. J. Immunol. 2010; 40: 1843-1851Crossref PubMed Scopus (292) Google Scholar). We hypothesized that this preferential localization might position mast cells to acquire IgE by a mechanism that requires cells to surmount the endothelial barrier. By using reporter IgE molecules, in vivo imaging techniques, and mast cell reporter mice, we demonstrate that perivascular mast cells dynamically extend processes into the vascular compartment to selectively acquire IgE from the blood. Passive diffusion of blood-borne IgE across the vasculature has been considered to be the primary means by which tissue mast cells acquire IgE. However, we hypothesized a more active mechanism of IgE acquisition by mast cells, which would lead to selective uptake of IgE by a subset of mast cells. Supporting this idea, ear skin mast cells from 6-week old 4get BALB/c mice, in which mast cells constitutively express enhanced green fluorescent protein (eGFP) (see Figure S1A available online; Gessner et al., 2005Gessner A. Mohrs K. Mohrs M. Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production.J. Immunol. 2005; 174: 1063-1072Crossref PubMed Scopus (231) Google Scholar), showed heterogeneous surface IgE with approximately 50% of the mast cells having high cell surface-bound IgE (Figure 1A). In contrast, peritoneal mast cells exhibited uniform cell-surface IgE. These differences were not a result of the protease-dependent skin mast cell isolation protocol as protease-treated peritoneal mast cells showed no loss of surface IgE (Figure S1B). Mast cell-bound IgE has a half-life of up to 2 weeks and can modulate mast cell expression of FcεRI (Gould and Sutton, 2008Gould H.J. Sutton B.J. IgE in allergy and asthma today.Nat. Rev. Immunol. 2008; 8: 205-217Crossref PubMed Scopus (836) Google Scholar; Yamaguchi et al., 1997Yamaguchi M. Lantz C.S. Oettgen H.C. Katona I.M. Fleming T. Miyajima I. Kinet J.P. Galli S.J. IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions.J. Exp. Med. 1997; 185: 663-672Crossref PubMed Scopus (390) Google Scholar). Therefore, we examined IgE uptake in IgE-deficient 4getxRag2−/− mice following intravenous (i.v.) infusion of 10 μg of IgE. Despite peak IgE titers more than 50-fold greater than physiologic levels in IgE-replete animals (data not shown), only a select population of ear skin mast cells demonstrated IgE uptake at 1 hr and continued to accumulate IgE throughout the time course (Figure 1B). In contrast, peritoneal mast cells showed uniform uptake of IgE at 1 hr and further accumulation of IgE throughout the time course, similar to profiles seen at steady state in wild-type (WT) animals. The ear skin mast cells also did not demonstrate surface IgE staining commensurate with peritoneal mast cells. Although slightly lower than on peritoneal mast cells, FcεRI expression on skin mast cells could not account for this discrepancy (Figure 1C). Similar results were obtained with a smaller 1 μg infusion but with markedly lower IgE uptake in the ear (Figure S1C). Together, these data suggested that skin blood vessels regulate IgE trafficking into the tissue and that select mast cell populations had greater access to vascular contents. The data predicted that IgE uptake would similarly localize to perivascular mast cells. To visualize IgE uptake in tissues, we constructed a reporter IgE molecule consisting of a tandem red fluorescent protein (tdRFP) fused N-terminal to the Cε2–Cε4 domains of the IgE heavy chain (Cheng et al., 2010Cheng L.E. Wang Z.E. Locksley R.M. Murine B cells regulate serum IgE levels in a CD23-dependent manner.J. Immunol. 2010; 185: 5040-5047Crossref PubMed Scopus (42) Google Scholar). The resulting homodimeric surrogate IgE molecule has a similar molecular weight as native IgE (188 kDa versus ∼200 kDa for native IgE). After an i.v. infusion, RFP-Fcε was found on the cell surface of FcεRI+ cells, including splenic basophils and peritoneal mast cells (Figure 2A). Additionally, gating of peritoneal exudate cells and total splenocytes on RFP+ cells revealed that essentially all of these cells were mast cells or basophils, respectively (Figure 2B). Similar to data with native IgE, only a subset of skin mast cells captured RFP-Fcε after a 10 μg i.v. infusion (Figure 2C). Together, these data indicated that RFP-Fcε displays similar binding and distribution characteristics to native IgE. To visualize the distribution of mast cell IgE uptake, we infused 10 μg RFP-Fcε i.v. into WT or mast cell-deficient KitW-sh/W-sh (Sash) mice (Wolters et al., 2005Wolters P.J. Mallen-St Clair J. Lewis C.C. Villalta S.A. Baluk P. Erle D.J. Caughey G.H. Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice.Clin. Exp. Allergy. 2005; 35: 82-88Crossref PubMed Scopus (132) Google Scholar). After 24 hr, we counterstained blood vessels in vivo with i.v. tomato lectin FITC and examined whole mounts of ear tissue by using confocal microscopy (Figure 3A). WT mice showed an abundance of RFP+ cells with most cells lying in a perivascular location. In contrast to WT mice, mast cell-deficient mice demonstrated no RFP+ cells in the ear skin, though RFP+ basophils could be demonstrated within the vasculature (Figure 3A). We next sought to obtain quantitative data to examine whether RFP+ mast cells tended to be closer to blood vessels than the total mast cell pool. When bred to a cre-dependent lineage reporter mouse, such as Rosa-YFP (Srinivas et al., 2001Srinivas S. Watanabe T. Lin C.S. William C.M. Tanabe Y. Jessell T.M. Costantini F. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.BMC Dev. Biol. 2001; 1: 4Crossref PubMed Scopus (2305) Google Scholar), MCPT5cre reporter mice (M5Rosa-YFP) allow specific visualization of >90% of mast cells within the ear skin (Dudeck et al., 2011Dudeck A. Dudeck J. Scholten J. Petzold A. Surianarayanan S. Köhler A. Peschke K. Vöhringer D. Waskow C. Krieg T. et al.Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens.Immunity. 2011; 34: 973-984Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar; Scholten et al., 2008Scholten J. Hartmann K. Gerbaulet A. Krieg T. Müller W. Testa G. Roers A. Mast cell-specific Cre/loxP-mediated recombination in vivo.Transgenic Res. 2008; 17: 307-315Crossref PubMed Scopus (152) Google Scholar). After infusion with RFP-Fcε, RFP-Fcε was found on ∼50% of mast cells (Figure 3B), and some RFP-Fcε+ mast cells appeared to direct cellular projections toward the blood vessel though these initial studies lacked the resolution to define these projections (Figure 3C). Whereas RFP-Fcε+ and RFP-Fcε− mast cells were both found to associate with the vasculature, RFP+ mast cells were on average 35% closer to the nearest blood vessel compared to the total mast cell population (Figure 3D). In addition, nearly half of the RFP+ cells were within 2 μm of the nearest blood vessel, whereas only one quarter of the total mast cell population was similarly positioned (Figure 3D). Together, these data indicated that perivascular mast cells preferentially acquire IgE from the blood, and we hypothesized that mast cells might directly sample blood to acquire IgE. We first took a flow cytometric approach to demonstrate that mast cells have direct access to blood contents. Similar to established approaches (Pereira et al., 2009Pereira J.P. An J. Xu Y. Huang Y. Cyster J.G. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.Nat. Immunol. 2009; 10: 403-411Crossref PubMed Scopus (167) Google Scholar; Zachariah and Cyster, 2010Zachariah M.A. Cyster J.G. Neural crest-derived pericytes promote egress of mature thymocytes at the corticomedullary junction.Science. 2010; 328: 1129-1135Crossref PubMed Scopus (156) Google Scholar), we infused 4get mice with a c-kit monoclonal antibody (2B8) conjugated to a high molecular weight fluorophore, phycoerythrin (PE). If allowed to circulate for a short period of time, PE-antibody conjugates remain intravascular and binding to target cells requires either direct blood exposure or sampling of intravascular contents. After a 5 min infusion, we observed that approximately 15%–20% of mast cells captured 2B8-PE (Figure 4A). Capture of 2B8-PE was not IgE-dependent because Fcer1a−/− mice showed similar 2B8-PE uptake when compared to WT animals. As noted in our prior experiments, peritoneal mast cells display rapid and uniform acquisition of IgE (Figure 1). To examine whether peritoneal mast cells similarly display direct access to the blood, we assessed 2B8-PE binding in these cells. Consistent with a lack of direct access to the blood and in contrast to ear skin mast cells, peritoneal mast cells showed no binding of 2B8-PE after i.v. exposure (Figure 4B). This was not due to an inherent inability to bind this antibody because intraperitoneal (i.p.) injection of 2B8-PE led to rapid binding to peritoneal mast cells but essentially no binding to skin mast cells (Figure 4B). We next sought to characterize the positioning and dynamics of mast cell projections and blood vessels (Figure 3B). To investigate this, we employed intravital, high-resolution confocal microscopy in MCPT5-cre x Ai6 mice (M5Ai6), which allowed for greater detail in visualization of mast cells and cellular projections in vivo (Madisen et al., 2010Madisen L. Zwingman T.A. Sunkin S.M. Oh S.W. Zariwala H.A. Gu H. Ng L.L. Palmiter R.D. Hawrylycz M.J. Jones A.R. et al.A robust and high-throughput Cre reporting and characterization system for the whole mouse brain.Nat. Neurosci. 2010; 13: 133-140Crossref PubMed Scopus (3847) Google Scholar). Similar to our static imaging, we found mast cells closely approximated to blood vessels marked with labeled anti-CD31 antibody (Figure 5A). We observed two distinct probing phenomena. First, some mast cells demonstrated relatively stable projections in the interior of blood vessels (Figure 5A; Movie S1). As we followed such cells in time, serial images demonstrated the retraction of projections (Figure 5B; Movie S2). In Figure 5B, the projection retracted approximately 5 μm over 30 min. We also noted a second behavior in which mast cells serially interacted with the vessel wall and/or the interior of the lumen with portions of the cell body or a cellular projection (Figure 5C; Movie S3). Because mast cells would not be expected to penetrate blood vessels ensheathed in smooth muscle, including arterioles, we also examined the distribution of mast cells in relation to smooth muscle actin (SMA)-positive vessels. Ear skin whole-mount tissue demonstrated a relative paucity of SMA+ blood vessels at the periphery of the ear where we performed dynamic imaging (Figure S2A). These data indicate that distal ear skin primarily contains capillary beds and smaller venules. Consistent with the representation of SMA+ vessels in the ear skin, mast cells showed a relative absence of disposition toward these vessels as ∼3% of mast cells were positioned within 2 μm of SMA+ vessels compared to ∼25% found disposed near CD31+ blood vessels in general (Figure S2B). We next examined whether mast cells with recent IgE uptake showed a similar pattern of IgE uptake. After infusion with RFP-Fcε, we stained fixed ear tissue for SMA. Though our analysis was limited by a drop in RFP signal following fixation, we observed that RFP+ cells tended to be in locations remote from SMA+ vessels (Figure S2C). We next examined fixed ear tissue to further define the entry point of the cellular extensions at the blood vessels. After a brief period of labeling blood vessels in vivo with anti-CD31 monoclonal antibody, we harvested ear tissue and analyzed fixed tissue by using confocal microscopy on ear skin whole mounts. Optical sectioning of the tissue indicated that extensions from the mast cell entered the blood vessel at areas with diminished CD31 staining, suggesting penetration of the vessel lumen (Figures 5D and 5E). In Figure 5E, the extension makes an abrupt turn as it traverses the vessel wall and then associates with the lumen of the vessel wall. Although our data indicated that mast cell sampling of blood contents is an efficient means for perivascular mast cells to capture free IgE, other mechanisms could also contribute. Loading of monomeric IgE onto mast cells is thought to modulate mast cell function, including the possibility of piecemeal degranulation (Kawakami and Galli, 2002Kawakami T. Galli S.J. Regulation of mast-cell and basophil function and survival by IgE.Nat. Rev. Immunol. 2002; 2: 773-786Crossref PubMed Scopus (522) Google Scholar), which could lead to local changes in vasopermeability and increased IgE diffusion. By using cell surface CD107a and diminished side-scatter profile as markers of mast cell activation and degranulation, we examined whether IgE loading on mast cells resulted in changes in either of these parameters (Gekara and Weiss, 2008Gekara N.O. Weiss S. Mast cells initiate early anti-Listeria host defences.Cell. Microbiol. 2008; 10: 225-236PubMed Google Scholar). To ensure uniform loading of mast cells during the assay, we used peritoneal mast cells as our source of mast cells. Following an i.v. infusion of IgE, peritoneal mast cells demonstrated baseline expression of CD107a and native SSC profiles, which contrasted with control antigen-IgE-activated mast cells (Figure 6A). To directly address the importance of secreted mast cell products, such as histamine, on IgE uptake in skin, we used a pharmacologic approach to block H1 and H2 histamine receptors and mast cell degranulation. IgE loading in ear skin mast cells was not affected by these inhibitors (Figure 6B). We next wanted to determine whether mast cell projections directly interact with intravascular IgE. Because fluorescence of RFP-Fcε was too insensitive for this application, we developed a technique by using streptavidin-coated beads coupled to biotinylated IgE and a fluorescent dye. After an infusion of 109 beads, beads were found in systemic circulation but were cleared within 15 min (data not shown). As a control, we used dye-coated beads. After infusion of control beads into mast cell reporter mice, we found a few beads near perivascular mast cells but no interaction with the bead (Figure 7A; Movie S4). In contrast, mast cells showed interactions with IgE-coated beads in the form of projections extending toward an intravascular bead and engulfing it (Figure 7B; Movies S5 and S6). To further establish the capacity of mast cells to capture intravascular IgE, we determined the number of IgE-coated beads in mouse ear skin 20 min after infusion. In mast cell replete mice, we recovered an average of 1,337 beads per mg of ear tissue (Figure 7C). In contrast, mast cell deficient (MCPT5cre x Rosa-DTA) mice exhibited a nearly 70% drop in bead recovery. Together, these data indicate that mast cells interact directly with intravascular contents in a dynamic fashion and selectively remove IgE from blood. The acquisition of IgE by mast cells is central to mast cell function, and the importance of this interaction has been underscored by two recent studies (Dudeck et al., 2011Dudeck A. Dudeck J. Scholten J. Petzold A. Surianarayanan S. Köhler A. Peschke K. Vöhringer D. Waskow C. Krieg T. et al.Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens.Immunity. 2011; 34: 973-984Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar; Feyerabend et al., 2011Feyerabend T.B. Weiser A. Tietz A. Stassen M. Harris N. Kopf M. Radermacher P. Möller P. Benoist C. Mathis D. et al.Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.Immunity. 2011; 35: 832-844Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar). Given the critical role of IgE in mast cell biology, our study sought to examine how tissue mast cells acquire IgE. The studies presented here indicate that IgE acquisition by mast cells is regulated at the level of the vasculature with perivascular mast cells demonstrating selective uptake of IgE from the blood. Further understanding into the regulation of mast cell IgE uptake may also provide new therapeutic approaches, as well. Immune surveillance of intravascular components has been previously described in professional antigen presenting cells (APC), including intra-aortic dendritic cells and Kupffer cells, which also reside within the vasculature (Choi et al., 2009Choi J.H. Do Y. Cheong C. Koh H. Boscardin S.B. Oh Y.S. Bozzacco L. Trumpfheller C. Park C.G. Steinman R.M. Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves.J. Exp. Med. 2009; 206: 497-505Crossref PubMed Scopus (198) Google Scholar; Lee et al., 2010Lee W.Y. Moriarty T.J. Wong C.H. Zhou H. Strieter R.M. van Rooijen N. Chaconas G. Kubes P. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells.Nat. Immunol. 2010; 11: 295-302Crossref PubMed Scopus (251) Google Scholar). Our data illustrate that extravascular cells are also capable of probing blood, akin to sampling of intraluminal contents in the gastrointestinal and respiratory tracts by CD103+ dendritic cells (Chieppa et al., 2006Chieppa M. Rescigno M. Huang A.Y. Germain R.N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement.J. Exp. Med. 2006; 203: 2841-2852Crossref PubMed Scopus (577) Google Scholar; Lambrecht and Hammad, 2009Lambrecht B.N. Hammad H. Biology of lung dendritic cells at the origin of asthma.Immunity. 2009; 31: 412-424Abstract Full Text Full Text PDF PubMed Scopus (288) Google Scholar; Rescigno et al., 2001Rescigno M. Urbano M. Valzasina B. Francolini M. Rotta G. Bonasio R. Granucci F. Kraehenbuhl J.P. Ricciardi-Castagnoli P. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria.Nat. Immunol. 2001; 2: 361-367Crossref PubMed Scopus (2025) Google Scholar). Mast cells are not generally considered to be antigen-presenting cells, though mast cells may express MHC class II under specific conditions (Kambayashi et al., 2009Kambayashi T. Allenspach E.J. Chang J.T. Zou T. Shoag J.E. Reiner S.L. Caton A.J. Koretzky G.A. Inducible MHC class II expression by mast cells supports effector and regulatory T cell activation.J. Immunol. 2009; 182: 4686-4695Crossref PubMed Scopus (118) Google Scholar). Instead, intravascular sampling appears to be a means for mast cells to capture unbound IgE, which in turn could promote mast cell function and survival (Kawakami and Galli, 2002Kawakami T. Galli S.J. Regulation of mast-cell and basophil function and survival by IgE.Nat. Rev. Immunol. 2002; 2: 773-786Crossref PubMed Scopus (522) Google Scholar; Kraft and Kinet, 2007Kraft S. Kinet J.P. New developments in FcepsilonRI regulation, function and inhibition.Nat. Rev. Immunol. 2007; 7: 365-378Crossref PubMed Scopus (452) Google Scholar). Tissue mast cells have long been known to project dendrites, although the function of these projections has not been clear. Beyond sampling blood, mast cells may also extend projections for intercellular communication through a network of cytonemes. The significance of these projections has not been examined in vivo (Fifadara et al., 2010Fifadara N.H. Beer F. Ono S. Ono S.J. Interaction between activated chemokine receptor 1 and FcepsilonRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells.Int. Immunol. 2010; 22: 113-128Crossref PubMed Scopus (35) Google Scholar). We speculate that in addition to capturing IgE, mast cells employ this sampling mechanism as part of a sentinel function in host defense. Localization to barrier surfaces, the capacity to induce immediate inflammatory responses, and the ability to recruit additional immune cells, positions mast cells as initial responders to pathogen invasion. Specific IgE further enhances these functions when antigen is present. Although local production of IgE has been described in the airway mucosa (Gould and Sutton, 2008Gould H.J. Sutton B.J. IgE in allergy and asthma today.Nat. Rev. Immunol. 2008; 8: 205-217Crossref PubMed Scopus (836) Google Scholar), delivery to the skin and mucosal sites remote from IgE production requires systemic distribution. The surveillance mechanism we describe limits distribution of IgE to subsets of mast cells in close approximation to the vasculature. Thus, the cells most likely to influence vascular permeability after activation also have the greatest access to free IgE. It remains unclear whether this anatomic positioning also defines subsets of mast cells that have functional differences beyond the effects of IgE. Our studies focus on the steady-state means by which mast cells acquire IgE. Local changes in vascular permeability, which could be seen with immediate hypersensitivity reactions, infection, or dermatitis, may further modulate IgE loading. In addition, the disparate mechanisms by which skin and peritoneal mast cells acquire IgE suggest that IgE uptake may be organ-specific. Several factors, including mast cell positioning, local vascular permeability, and the predominant mast cell populations (connective tissue versus mucosal) contained within each organ may all play a role in IgE acquisition. Our data uncover a regulated means by which mast cells acquire IgE and fill an important gap in our understanding of the steps required in the elicitation of hypersensiti" @default.
• W2023877563 created "2016-06-24" @default.
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• W2023877563 date "2013-01-01" @default.
• W2023877563 modified "2023-09-29" @default.
• W2023877563 title "Perivascular Mast Cells Dynamically Probe Cutaneous Blood Vessels to Capture Immunoglobulin E" @default.
• W2023877563 cites W1576093064 @default.
• W2023877563 cites W1650320961 @default.
• W2023877563 cites W1699053637 @default.
• W2023877563 cites W1845975704 @default.
• W2023877563 cites W1953360647 @default.
• W2023877563 cites W1970152214 @default.
• W2023877563 cites W1970166280 @default.
• W2023877563 cites W1986542865 @default.
• W2023877563 cites W1989607865 @default.
• W2023877563 cites W2009342716 @default.
• W2023877563 cites W2025383736 @default.
• W2023877563 cites W2025442131 @default.
• W2023877563 cites W2030904598 @default.
• W2023877563 cites W2038948548 @default.
• W2023877563 cites W2040640809 @default.
• W2023877563 cites W2063906189 @default.
• W2023877563 cites W2067500883 @default.
• W2023877563 cites W2088553840 @default.
• W2023877563 cites W2090434004 @default.
• W2023877563 cites W2092646329 @default.
• W2023877563 cites W2101821813 @default.
• W2023877563 cites W2104135721 @default.
• W2023877563 cites W2105708181 @default.
• W2023877563 cites W2106301295 @default.
• W2023877563 cites W2109627278 @default.
• W2023877563 cites W2115734610 @default.
• W2023877563 cites W2127707940 @default.
• W2023877563 cites W2140856724 @default.
• W2023877563 cites W2145420458 @default.
• W2023877563 cites W2148159422 @default.
• W2023877563 cites W2154196772 @default.
• W2023877563 cites W2163851558 @default.
• W2023877563 doi "https://doi.org/10.1016/j.immuni.2012.09.022" @default.
• W2023877563 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3576928" @default.
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