Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22

Abstract

The maintenance of barrier function at exposed surfaces of the mammalian body is essential for limiting exposure to environmental stimuli, preventing systemic dissemination of commensal and pathogenic microbes and retaining normal homeostasis of the entire body. Indeed, dysregulated barrier function is associated with many infectious and inflammatory diseases, including psoriasis, influenza, inflammatory bowel disease and human immunodeficiency virus, which collectively afflict millions of people worldwide. Studies have shown that interleukin 22 (IL-22) is expressed at barrier surfaces and that its expression is dysregulated in certain human diseases, which suggests a critical role in the maintenance of normal barrier homeostasis. Consistent with that, studies of mouse model systems have identified a critical role for signaling by IL-22 through its receptor (IL-22R) in the promotion of antimicrobial immunity, inflammation and tissue repair at barrier surfaces. In this review we will discuss how the expression of IL-22 and IL-22R is regulated, the functions of the IL-22-IL-22R pathway in regulating immunity, inflammation and tissue homeostasis, and the therapeutic potential of targeting this pathway in human disease.

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…Steady‐state ILC3 are the dominant source of IL‐22, a cytokine that acts on non‐haematopoietic cells including intestinal epithelial cells 8. IL‐22 signalling induces a cascade of gene expression in epithelial cells typified by the secretion of antimicrobial peptides such as RegIII proteins, S100a8 and S100a9 8, 77.…”

Innate Lymphoid Cells in Graft-Versus-Host Disease

“…Innate lymphoid cells (ILC) are effector cells contributing to the early immune responses against microbes 1, stimulating tissue regeneration 2 and strengthening the epithelial barrier at mucosal surfaces 3. A detailed description of the tissue‐specific functions of the human ILC subsets have recently been provided elsewhere 4.…”

CARD9 et colite : un pont entre dysbiose et immunité

“…Le microbiote intestinal humain est un écosystème complexe composé de plus de 10 11 microorganismes par gramme de fèces. Il joue un rôle crucial dans de nombreuses fonctions vitales comme la digestion, le déve-loppement du système immunitaire [20] (➜), la lutte contre les organismes pathogènes [21] [11,12]. De plus, nous avons montré récemment qu'il existe, au niveau des cellules épithéliales intestinales des souris Card9 -/-, une diminution de la prolifération et une augmentation de l'apoptose à la suite d'une colite induite par le DSS [13].…”

“…Il a également été observé chez ces animaux une diminution de l'expression de Reg3 et Reg3 au niveau colique et une altération du microbiote intestinal bactérien et fongique [13]. Ces données confirment l'importance de CARD9 au niveau de l'intestin dans l'immunité, le maintien d'un microbiote [11,14]. Un marquage et des analyses de ces différentes cellules par cytométrie en flux nous ont permis de montrer que le microbiote des souris Card9 -/-est incapable d'induire la production d'IL-22 par les cellules T et les CLI du côlon, ce qui provoque une susceptibilité accrue à la colite [13].…”