IL-18 is required for the TH1-adaptation of TREG cells and the selective suppression of TH17 responses in acute and chronic infections

被引：11

作者：

Alvarez, Fernando ^{[1
,2
,3
]}

Istomine, Roman ^{[1
,2
,3
]}

Filho, Alonso Da Silva Lira ^{[1
]}

Al-Aubodah, Tho-Alfakar ^{[1
,2
,3
]}

Huang, Daniel ^{[1
,2
,3
]}

Okde, Rakan ^{[1
,2
,3
]}

Olivier, Martin ^{[1
]}

Fritz, Jorg H. ^{[1
,3
,4
]}

Piccirillo, Ciriaco A. ^{[1
,2
,3
,4
]}

机构：

[1] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada

[2] Res Inst McGill Univ Hlth Ctr RI MUHC, Ctr Translat Biol, Program Infect Dis & Immunol Global Hlth, Montreal, PQ, Canada

[3] Ctr Excellence Translat Immunol CETI, Montreal, PQ, Canada

[4] McGill Univ Res Ctr Complex Traits MRCCT, Montreal, PQ, Canada

来源：

MUCOSAL IMMUNOLOGY | 2023年 / 16卷 / 04期

基金：

加拿大健康研究院;

关键词：

REGULATORY T-CELLS; A VIRUS-INFECTION; IFN-GAMMA; CYTOKINE MILIEU; TGF-BETA; DIFFERENTIATION; TH1; EXPRESSION; RECEPTOR; IL-33;

D O I：

10.1016/j.mucimm.2023.05.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interleukin (IL)-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs following influenza A (IAV) infections yet its role in orchestrating the local adaptive immune response remains ill defined. Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary TH1 responses but also influences regulatory T cells (TREG) function in the infected lungs. As the response unfolds, TREG cells accumulating in the lungs express Helios, T-bet, CXCR3, and IL 18R1 and produce interferon & gamma; in the presence of IL-12. During IAV, IL-18R1 is required for TREG cells to control TH17, but not TH1, responses and promote a return to lung homeostasis, revealing a novel mechanism of selective suppression. Moreover, this observation was not limited to the lungs, as skin-localized TREG cells require an IL-18 signal to specifically suppress IL-17A production by TH17 and & gamma;& delta; T cells in a model of chronic cutaneous Leishmania major infection. Overall, these results uncover how IL-18 orchestrates the tissue adaptation of TREG cells to selectively favor TH1 over TH17 responses during TH1-driven immune responses and provide a novel perspective into how IL-18 dictates the immune response during viral and parasitic infections.

引用

页码：462 / 475

页数：14

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