RRC ID 75013
Author Yamada T, Tatematsu M, Takasuga S, Fuchimukai A, Yamagata K, Seki S, Kuba K, Yoshida H, Taniuchi I, Bernhardt G, Shibuya K, Shibuya A, Yamada T, Ebihara T.
Title TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy.
Journal J Exp Med
Abstract While group-2 innate lymphoid cells (ILC2s) are highly proliferative in allergic inflammation, the removal of overactivated ILC2s in allergic diseases has not been investigated. We previously showed that chronic airway allergy induces "exhausted-like" dysfunctional ILC2s expressing T cell immunoreceptor with Ig and ITIM domains (TIGIT). However, the physiological relevance of these cells in chronic allergy remains elusive. To precisely identify and monitor TIGIT+ ILC2s, we generated TIGIT lineage tracer mice. Chronic allergy stably induced TIGIT+ ILC2s, which were highly activated, apoptotic, and were quickly removed from sites of chronic allergy. Transcripts from coding genes were globally suppressed in the cells, possibly due to reduced chromatin accessibility. Cell death in TIGIT+ ILC2s was enhanced by interactions with CD155 expressed on macrophages, whereas genetic ablation of Tigit or blockade by anti-TIGIT antagonistic antibodies promoted ILC2 survival, thereby deteriorating chronic allergic inflammation. Our work demonstrates that TIGIT shifts the fate of ILC2s toward activation-induced cell death, which could present a new therapeutic target for chronic allergies.
Volume 220(7)
Published 2023-7-3
DOI 10.1084/jem.20222005
PII 214016
PMID 37036426
PMC PMC10098142
MeSH Animals Cell Death Hypersensitivity* Immunity, Innate* Inflammation Lymphocytes Mice Receptors, Immunologic* / genetics
IF 11.743
Mice RBRC04944