Title | ILC3s control airway inflammation by limiting T cell responses to allergens and microbes. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Teng F, Tachó-Piñot R, Sung B, Farber DL, Worgall S, Hammad H, Lambrecht BN, Hepworth MR, Sonnenberg GF |
Journal | Cell Rep |
Volume | 37 |
Issue | 8 |
Pagination | 110051 |
Date Published | 2021 11 23 |
ISSN | 2211-1247 |
Keywords | Adaptive Immunity, Allergens, Animals, Asthma, CD4-Positive T-Lymphocytes, Cytokines, Female, Host Microbial Interactions, Humans, Immunity, Innate, Inflammation, Lung, Lymph Nodes, Lymphocytes, Male, Mice, Mice, Inbred C57BL, Pyroglyphidae, Respiration, Respiratory Hypersensitivity, Th17 Cells, Th2 Cells |
Abstract | Group 3 innate lymphoid cells (ILC3s) critically regulate host-microbe interactions in the gastrointestinal tract, but their role in the airway remains poorly understood. Here, we demonstrate that lymphoid-tissue-inducer (LTi)-like ILC3s are enriched in the lung-draining lymph nodes of healthy mice and humans. These ILC3s abundantly express major histocompatibility complex class II (MHC class II) and functionally restrict the expansion of allergen-specific CD4+ T cells upon experimental airway challenge. In a mouse model of house-dust-mite-induced allergic airway inflammation, MHC class II+ ILC3s limit T helper type 2 (Th2) cell responses, eosinophilia, and airway hyperresponsiveness. Furthermore, MHC class II+ ILC3s limit a concomitant Th17 cell response and airway neutrophilia. This exacerbated Th17 cell response requires exposure of the lung to microbial stimuli, which can be found associated with house dust mites. These findings demonstrate a critical role for antigen-presenting ILC3s in orchestrating immune tolerance in the airway by restricting pro-inflammatory T cell responses to both allergens and microbes. |
DOI | 10.1016/j.celrep.2021.110051 |
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Alternate Journal | Cell Rep |
PubMed ID | 34818549 |
PubMed Central ID | PMC8635287 |
Grant List | R01 AI162936 / AI / NIAID NIH HHS / United States R21 CA249274 / CA / NCI NIH HHS / United States P01 AI106697 / AI / NIAID NIH HHS / United States R01 AI145989 / AI / NIAID NIH HHS / United States R01 AI123368 / AI / NIAID NIH HHS / United States / WT_ / Wellcome Trust / United Kingdom R01 AI143842 / AI / NIAID NIH HHS / United States U01 AI095608 / AI / NIAID NIH HHS / United States 105644/Z/14/Z / WT_ / Wellcome Trust / United Kingdom BB/T014482/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom |