IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice

A. Visperas; J. S. Do; K. Bulek; X. Li; B. Min

doi:10.1038/mi.2013.82

IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice

A. Visperas, J. S. Do, K. Bulek, X. Li, B. Min^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1b and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1b production and Th17 differentiation. IL-27Ra/ T-cell receptor (TCR)b/ recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Ra/ TCRb/ recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Ra/ TCRb/ mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1b by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.

Original language	English (US)
Pages (from-to)	625-633
Number of pages	9
Journal	Mucosal Immunology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1038/mi.2013.82
State	Published - May 2014
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice",

abstract = "T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1b and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1b production and Th17 differentiation. IL-27Ra/ T-cell receptor (TCR)b/ recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Ra/ TCRb/ recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Ra/ TCRb/ mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1b by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.",

author = "A. Visperas and Do, {J. S.} and K. Bulek and X. Li and B. Min",

note = "Funding Information: We thank Ms Jennifer Powers for cell sorting, Dr Michael Freeman for scoring, and Drs Robert Fairchild, Bo Shen, Carol de la Motte, and Alex Huang for critical comments. This study was supported by NIH grants R01-AI074932 (B.M.) and T32-GM88088 (A.V.).",

year = "2014",

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doi = "10.1038/mi.2013.82",

language = "English (US)",

volume = "7",

pages = "625--633",

journal = "Mucosal Immunology",

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AU - Visperas, A.

AU - Do, J. S.

AU - Bulek, K.

AU - Li, X.

AU - Min, B.

N1 - Funding Information: We thank Ms Jennifer Powers for cell sorting, Dr Michael Freeman for scoring, and Drs Robert Fairchild, Bo Shen, Carol de la Motte, and Alex Huang for critical comments. This study was supported by NIH grants R01-AI074932 (B.M.) and T32-GM88088 (A.V.).

PY - 2014/5

Y1 - 2014/5

N2 - T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1b and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1b production and Th17 differentiation. IL-27Ra/ T-cell receptor (TCR)b/ recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Ra/ TCRb/ recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Ra/ TCRb/ mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1b by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.

AB - T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1b and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1b production and Th17 differentiation. IL-27Ra/ T-cell receptor (TCR)b/ recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Ra/ TCRb/ recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Ra/ TCRb/ mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1b by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.

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IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice

Abstract

ASJC Scopus subject areas

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