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• W2793171510 abstract "The now classical experiments reported by Medawar in the middle of the last century established the concept of an immune privilege for some sites: a transplant in the brain or eye of an autologous recipient could survive rejection, while the same tissue transplanted subcutaneously was swiftly rejected. These results suggested that the brain and the eye were somehow exempt from surveillance by immune cells. More broadly, these experiments hinted at the fact that, despite the existence of a circulating and supposedly autonomous immune system, local conditions mattered. Interestingly, while there is now strong evidence for some degree of immune surveillance in the brain, and as the notion of truly privileged sites has been called into question, the importance of local factors in shaping immune cell function has never been more relevant. First, we now know that many immune cells adapt to their tissue of residence. This is particularly true in the case of tissue-resident macrophages that derive from yolk sac progenitors and acquire distinct transcriptional programs as they differentiate into Langerhans cells in the skin, Kupffer cells in the liver, and microglia in the brain among many other cell types and locations. The gut is also home to many intraepithelial lymphocytes whose functions are adapted to the local environment, as reviewed by Van Kaer et al. in this issue. Second, it is also becoming increasingly clear that ‘typical’ immune responses differ from tissue to tissue, from their inception by distinct antigen-presenting cells, to their execution as some sites normally restrict the entry of activated T cells, to the memory phases of responses, where tissues shape resident memory cells. Some memory responses even appear to be dominated by resident cells, as shown recently by the MacKay and Masopust groups, further emphasizing the importance of the local milieu and players. In this special issue, we explore the immune specificities of distinct tissues through the angle of four distinct sites: the skin, the mouth, the eye, and the female genital tract, reviewed by Biedermann et al., Moutsopoulos et al., Dana et al., and Chen et al., respectively. Although this list cannot represent an exhaustive overview of the many types of local immune responses, it highlights a critical paradigm: the necessity to mitigate the effect of immune responses on normal tissue function. For example, clarity is critical at the ocular surface and excessive immune recruitment could compromise host sight, while mastication causes recurrent damage in the oral mucosa and this site is characterized by the constant presence of neutrophils. Even evolutionarily ancient responses, such as antiviral immunity, are modulated by the tissue in which they occur, as discussed by MacLeod et al. in these pages. These tissue ‘specificities’ raise two important points that are briefly introduced in this special issue but likely to be the subject of many pieces to come. From a theoretical point of view, Eberl and Pradeu discuss how the integration of tissue and organismal (i.e., metabolic and nervous) feedback may pave the way to a general theory of immunity that considers both local conditions and central immune paradigms and establish the immune system as a guardian of homeostasis, beyond mere pathogen control. This integration of antimicrobial and physiological responses was the subject of a recent publication by the Belkaid group, here previewed by Scharschmidt et al. From a more applied perspective, Opdenakker et al. review chronic wounds and highlight how a better understanding of normal and abnormal skin healing, as well as collaborations between dermatologists, immunologists, and surgeons and nurses, are critical to improve care. As immunology becomes more entangled with tissue biology, such collaborations are likely to play a critical role in improving care. Like the local economy, local immunity is now in vogue, and resources in development, like the Human Atlas and Immune Atlas, as well as the emergence of more refined models of local infection, will provide new avenues of research for years to come. I look forward seeing new developments in these areas and hope this special issue will serve as an inspiration for these fields. I want to thank all of the authors and especially the reviewers who contributed to the articles presented here. I also want to thank Shizuka Aoki and her team at BioRender (https://biorender.io/) for the graphical work done on the cover and several figures in this issue. Please feel free to send us your feedback about this issue at [email protected] or on @TrendsImmuno (https://twitter.com/TrendsImmuno)." @default.
• W2793171510 created "2018-03-29" @default.
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• W2793171510 date "2018-04-01" @default.
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• W2793171510 title "To Each his Own" @default.
• W2793171510 doi "https://doi.org/10.1016/j.it.2018.02.005" @default.
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