IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection

被引：165

作者：

Pelly, V. S. ^{[1
]}

Kannan, Y. ^{[1
]}

Coomes, S. M. ^{[1
]}

Entwistle, L. J. ^{[1
]}

Ruckerl, D. ^{[2
]}

Seddon, B. ^{[3
]}

MacDonald, A. S. ^{[4
]}

McKenzie, A. ^{[5
]}

Wilson, M. S. ^{[1
]}

机构：

[1] Francis Crick Inst, Mill Hill Lab, London, England

[2] Univ Edinburgh, 3IR, Edinburgh, Midlothian, Scotland

[3] UCL, Inst Immun & Transplantat, London, England

[4] Univ Manchester, Fac Life Sci, Manchester, Lancs, England

[5] Univ Cambridge, MRC Lab Mol Biol, Cambridge, England

来源：

MUCOSAL IMMUNOLOGY | 2016年 / 9卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

INNATE LYMPHOID-CELLS; TRANSCRIPTION FACTOR GATA3; CD4(+) T-CELLS; TYPE-2; IMMUNITY; MAST-CELLS; IL-4; INTERLEUKIN-4; IL-4R-ALPHA; EXPRESSION; RESPONSES;

D O I：

10.1038/mi.2016.4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (TH2) differentiation of CD4(+) T cells to elicit type-2 immunity. Despite a good understanding of the inflammatory cascade elicited following helminth infection, the initial source of IL-4 is unclear. Previous studies using the rat helminth parasite Nippostronglyus brasiliensis, identified an important role for basophil-derived IL-4 for T(H)2 differentiation. However, basophils are redundant for T(H)2 differentiation following infection with the natural helminth parasite of mice Heligmosomoides polygyrus, indicating that other sources of IL-4 are required. In this study using H. polygyrus, which is controlled by IL-4-dependent immunity, we identified that group-2 innate lymphoid cells (ILC2s) produced significant amounts of IL-4 and IL-2 following H. polygyrus infection. Leukotriene D4 was sufficient to stimulate IL-4 secretion by ILC2s, and the supernatant from activated ILC2s could potently drive T(H)2 differentiation in vitro in an IL-4-dependent manner. Furthermore, specific deletion of IL-4 from ILC2s compromised T(H)2 differentiation in vivo. Overall, this study highlights a previously unrecognized and important role for ILC2-derived IL-4 for T(H)2 differentiation in a natural T(H)2-dependent model of human helminthiasis.

引用

页码：1407 / 1417

页数：11