Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

Abstract

Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

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.…”

“…Additionally, ILC2 produce amphiregulin, which is crucial in tissue regeneration 2. For the development and function of human and mouse ILC2, the transcription factors GATA3 and RORα are essential 17.…”

“…For the development and function of human and mouse ILC2, the transcription factors GATA3 and RORα are essential 17. In the peripheral blood, the majority of CD127 + ILC are ILC2, additionally, group 2 ILC have been found in the healthy human lung 2, 18 and in the skin 19, 20. An updated view on ILC2 function in pulmonary and dermal inflammatory diseases is provided elsewhere 21.…”

“…All together, variable effects had been reported about Th2 cytokines. Interestingly, at least in mice, ILC2 produce the EGF‐related factor amphiregulin, which was shown to trigger epithelial tissue repair and restore lung tissue homeostasis after influenza virus infection 2. This notion suggests that ILC2 could possibly affect the sensitivity to GVHD via boosting epithelial cell regeneration after the conditioning therapy‐induced tissue damage.…”

Les cellules lymphoïdes innées

“…Au niveau pulmonaire, les ILC2 provoquent une inflammation d'origine éosinophilique induite contre Strongyloides venezuelensis [23]. Les ILC2 sont aussi source d'amphiréguline, une protéine qui participe au maintien de la fonction pulmonaire après une infection par le virus de la grippe [38]. Enfin, des ILC2 « inflammatoires », qui produisent de l'IL-17, participent à la réponse immunitaire lors d'une infection par la levure Candida albicans [18].…”