Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

被引：207

作者：

Halim, Timotheus Y. F. ^{[1
,2
]}

Rana, Batika M. J. ^{[1
]}

Walker, Jennifer A. ^{[1
]}

Kerscher, Bernhard ^{[1
,10
]}

Knolle, Martin D. ^{[1
,3
]}

Jolin, Helen E. ^{[1
]}

Serrao, Eva M. ^{[2
]}

Haim-Vilmovsky, Liora ^{[4
]}

Teichmann, Sarah A. ^{[4
]}

Rodewald, Hans-Reimer ^{[5
]}

Botto, Marina ^{[6
]}

Vyse, Timothy J. ^{[7
]}

Fallon, Padraic G. ^{[8
]}

Li, Zhi ^{[9
]}

Withers, David R. ^{[9
]}

McKenzie, Andrew N. J. ^{[1
]}

机构：

[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England

[2] Univ Cambridge, CRUK Cambridge Inst, Cambridge CB2 0RE, England

[3] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England

[4] Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton CB10 1SA, England

[5] German Canc Res Ctr, Div Cellular Immunol, D-69120 Heidelberg, Germany

[6] Imperial Coll London, Dept Med, London, England

[7] Kings Coll London, Dept Med & Mol Genet, London, England

[8] Trinity Coll Dublin, Trinity Biomed Sci Inst, Dublin, Ireland

[9] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England

[10] Paul Ehrlich Inst, Div Microbiol, Langen, Germany

来源：

IMMUNITY | 2018年 / 48卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

REGULATORY T-CELLS; TRANSCRIPTION FACTOR GATA3; ALLERGIC INFLAMMATION; LIGAND INTERACTION; GENE-EXPRESSION; MURINE MODEL; RESPONSES; ACTIVATION; ALPHA; INTERLEUKIN-33;

D O I：

10.1016/j.immuni.2018.05.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarm-ininduced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7ra(Cre/+)Tnfsf4(fl/fl) mice). Moreover, Il7ra(Cre/+) Tnfsf4(fl/fl) mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

引用

页码：1195 / +

页数：19

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