Induction and molecular signature of pathogenic T H 17 cells

Youjin Lee; Amit Awasthi; Nir Yosef; Francisco J. Quintana; Sheng Xiao; Anneli Peters; Chuan Wu; Markus Kleinewietfeld; Sharon Kunder; David A. Hafler; Raymond A. Sobel; Aviv Regev; Vijay K. Kuchroo

doi:https://doi.org/10.1038/ni.2416

Induction and molecular signature of pathogenic T H 17 cells

Youjin Lee, Amit Awasthi, Nir Yosef, Francisco J. Quintana, Sheng Xiao, Anneli Peters, Chuan Wu, Markus Kleinewietfeld, Sharon Kunder, David A. Hafler, Raymond A. Sobel, Aviv Regev, Vijay K. Kuchroo

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

Abstract

Interleukin 17 (IL-17)-producing helper T cells (T_H17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that T_H17 cells are main drivers of autoimmune tissue injury. However, not all T_H17 cells are pathogenic; in fact, T_H17 cells generated with transforming growth factor-α1 (TGF-α1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-α3 by developing T_H17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic T_H17 cells. Moreover, TGF-α3-induced T_H17 cells were functionally and molecularly distinct from TGF-α1-induced T_H17 cells and had a molecular signature that defined pathogenic effector T_H17 cells in autoimmune disease.

Original language	English
Pages (from-to)	991-999
Number of pages	9
Journal	Nature Immunology
Volume	13
Issue number	10
Early online date	9 Sep 2012
DOIs	https://doi.org/10.1038/ni.2416
State	Published - Oct 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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https://doi.org/10.1038/ni.2416

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title = "Induction and molecular signature of pathogenic T H 17 cells",

abstract = "Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-α1 (TGF-α1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-α3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-α3-induced TH17 cells were functionally and molecularly distinct from TGF-α1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.",

author = "Youjin Lee and Amit Awasthi and Nir Yosef and Quintana, {Francisco J.} and Sheng Xiao and Anneli Peters and Chuan Wu and Markus Kleinewietfeld and Sharon Kunder and Hafler, {David A.} and Sobel, {Raymond A.} and Aviv Regev and Kuchroo, {Vijay K.}",

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doi = "https://doi.org/10.1038/ni.2416",

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AU - Lee, Youjin

AU - Awasthi, Amit

AU - Yosef, Nir

AU - Quintana, Francisco J.

AU - Xiao, Sheng

AU - Peters, Anneli

AU - Wu, Chuan

AU - Kleinewietfeld, Markus

AU - Kunder, Sharon

AU - Hafler, David A.

AU - Sobel, Raymond A.

AU - Regev, Aviv

AU - Kuchroo, Vijay K.

PY - 2012/10

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N2 - Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-α1 (TGF-α1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-α3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-α3-induced TH17 cells were functionally and molecularly distinct from TGF-α1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.

AB - Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that TH17 cells are main drivers of autoimmune tissue injury. However, not all TH17 cells are pathogenic; in fact, TH17 cells generated with transforming growth factor-α1 (TGF-α1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-α3 by developing TH17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic TH17 cells. Moreover, TGF-α3-induced TH17 cells were functionally and molecularly distinct from TGF-α1-induced TH17 cells and had a molecular signature that defined pathogenic effector TH17 cells in autoimmune disease.

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SN - 1529-2908

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SP - 991

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JO - Nature Immunology

JF - Nature Immunology

IS - 10

ER -

Induction and molecular signature of pathogenic T H 17 cells

Abstract

All Science Journal Classification (ASJC) codes

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