Blocking CD226 regulates type 2 innate lymphoid cell effector function and alleviates airway hyperreactivity

被引：14

作者：

Sakano, Yoshihiro ^{[1
]}

Sakano, Kei ^{[1
]}

Hurrell, Benjamin P. ^{[1
]}

Helou, Doumet Georges ^{[1
]}

Shafiei-Jahani, Pedram ^{[1
]}

Kazemi, Mohammad H. ^{[1
]}

Li, Xin ^{[1
]}

Shen, Stephen ^{[1
]}

Hilser, James R. ^{[2
,3
]}

Hartiala, Jaana A. ^{[2
,3
]}

Allayee, Hooman ^{[2
,3
]}

Barbers, Richard ^{[4
]}

Akbari, Omid ^{[1
]}

机构：

[1] Univ Southern Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, NRT 5505,1450 Biggy St, Los Angeles, CA 90033 USA

[2] Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA 90033 USA

[3] Univ Southern Calif, Keck Sch Med, Dept Biochem & Mol Med, Los Angeles, CA 90033 USA

[4] Univ Southern Calif, Keck Sch Med, Dept Clin Med, Div Pulm & Crit Care Med, Los Angeles, CA 90033 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2024年 / 153卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Type 2 innate lymphoid cells; CD226; asthma; allergy; airway hyperreactivity; DNAM-1; ACTIVATION; EXPRESSION; INDUCTION; LFA-1;

D O I：

10.1016/j.jaci.2024.01.003

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 fndings 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 fndings underscore the potential of CD226 as a novel therapeutic target in ILC2s, presenting a promising avenue for ameliorating AHR and allergic asthma. (J Allergy Clin Immunol 2024;153:1406-22.)

引用

页码：1406 / 1422.e6

页数：23

共 62 条

[31] Severe asthma ILC2s demonstrate enhanced proliferation that is modified by biologics [J].