Critical regulation of early Th17 cell differentiation by IL-1 signaling

By Yeonseok Chung, S. Chang, G. Martinez, Xuexian O. Yang, R. Nurieva, H. Kang, Li Ma, S. Watowich, A. Jetten, Qiang Tian and 1 more. Immunity, 2009

1,215 citations recorded by the source corpus.

SUMMARY Th17 cells have been recently discovered in both mouse and human. Although IL-1 has been shown to be important in human Th17 cell differentiation with little knowledge of the underlying mechanism, its function in mouse is less clear. Here we show that IL-1R1 expression in T cells, which was induced by IL-6, was necessary for Th17-mediated autoimmunity and for early Th17 differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 differentiation from naïve or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 differentiation and maintain cytokine expression in effector Th17 cells. Importantly, IL-1 regulated the expression of IRF4 and RORγt during Th17 differentiation; over-expression of these two factors resulted in IL-1-independent Th17 polarization. Our data thus indicate a critical role of IL-1 in Th17 differentiation and this pathway may serve as a novel target for Th17-mediated immunopathology.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/1bb3aab4fb9a0aea75284db196de75201ef885d6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. W. E. Paul
2. Jinfang Zhu
3. C. Dong
4. C. Mauri
5. Yeonseok Chung
6. Xuexian O. Yang
7. F. Powrie
8. K. Mills

Citations in the corpus

• Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. (2009, background): “However, it has recently been reported that IL-1 signaling is critical for Th17 cell differentiation (Chung et al., 2009).”
• Autoimmune T cell responses in the central nervous system (2009, background): “Research efforts then focused on T H 17 cells, the differentiation of which depends on signalling mediated by transforming growth factor-β ( TGFβ ), IL-6 , IL-1 (Ref”
• Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) (2011, background): “Although IL-6 and TGF-b1 can efficiently induce IL-17 production, IL-6 together with IL-23 and IL-1b, in the absence of TGF-b1, also can induce IL-17 in naive Th cells (50, 51, 67).”
• The IL-1 family: regulators of immunity (2010, background): “Effects on adaptive immune cells IL-1 has been known for a long time to promote T cell responses, but recent findings have identified a key role for IL-1 in the differentiation of T H 17 cell”
• Th17 cells promote cytotoxic T cell activation in tumor immunity (2009, methodology): “1 OT-II transgenic mice were differentiated into Th17 effector cells in vitro (Chung et al., 2009; Nurieva et al., 2009).”
• Differentiation of Effector CD4 T Cell Populations (2010, neutral): “With the growing body of data indicating an important role for IL-1β in Th17 differentiation or stabilization (47, 306), there will be an interest in mutations affecting IL-1β production, such as those in the inflammasome pathway or in caspsase 1.”
• Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “IL-1 and tumor necrosis factor-a (TNFa) are important inflammatory cytokines and IL-1 has been shown critical for the differentiation of Th17 cells, especially in humans (33, 42, 43).”
• Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses (2010, neutral): “A recent study demonstrated that IL-1 stimulation results in IL-17 production in CD4+ T cells including Foxp3+ Treg cells (Chung et al., 2009).”
• Intestinal homeostasis and its breakdown in inflammatory bowel disease (2011, result): “This hypothesis is consistent with the ability of IL-1β and IL-18 to promote T H 17 and T H 1 responses, respectivel”
• THE INTERLEUKIN-1 FAMILY: BACK TO THE FUTURE (2013, neutral): “Accordingly, IL-1 is required for development of Th17 cell-sustained autoimmunity (e.g., Chung et al., 2009; Sutton et al., 2006; Veldhoen et al., 2006).”