Blocking CD226 regulates type 2 innate lymphoid cell effector function and alleviates airway hyperreactivity - 03/05/24
Graphical abstract |
Abstract |
Background |
Type 2 innate lymphoid cells (ILC2s) play a pivotal role in type 2 asthma. CD226 is a costimulatory molecule involved in various inflammatory diseases.
Objective |
We aimed to investigate CD226 expression and function within human and mouse ILC2s, and to assess the impact of targeting CD226 on ILC2-mediated airway hyperreactivity (AHR).
Methods |
We administered IL-33 intranasally to wild-type mice, followed by treatment with anti-CD226 antibody or isotype control. Pulmonary ILC2s were sorted for ex vivo analyses through RNA sequencing and flow cytometry. Next, we evaluated the effects of CD226 on AHR and lung inflammation in wild-type and Rag2−/− mice. Additionally, we compared peripheral ILC2s from healthy donors and asthmatic patients to ascertain the role of CD226 in human ILC2s.
Results |
Our findings demonstrated an inducible expression of CD226 in activated ILC2s, enhancing their cytokine secretion and effector functions. Mechanistically, CD226 alters intracellular metabolism and enhances PI3K/AKT and MAPK signal pathways. Blocking CD226 ameliorates ILC2-dependent AHR in IL-33 and Alternaria alternata–induced models. Interestingly, CD226 is expressed and inducible in human ILC2s, and its blocking reduces cytokine production. Finally, we showed that peripheral ILC2s in asthmatic patients exhibited elevated CD226 expression compared to healthy controls.
Conclusion |
Our findings underscore the potential of CD226 as a novel therapeutic target in ILC2s, presenting a promising avenue for ameliorating AHR and allergic asthma.
Le texte complet de cet article est disponible en PDF.Key words : Type 2 innate lymphoid cells, CD226, asthma, allergy, airway hyperreactivity
Abbreviations used : AHR, AKT, APC, ATP, BAL, DAPI, FA, FACS, FITC, hILC2, ILC2, IPA, LD, MAPK, NF-κB, NK, PBMC, PE, PI3K, rh, rm, RNA-Seq, Treg, WT
Plan
Vol 153 - N° 5
P. 1406 - mai 2024 Retour au numéro
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