Interleukin 23 receptor is essential for terminal differentiation of effector T helper type 17 cells in vivo

By M. McGeachy, Yi Chen, C. Tato, A. Laurence, B. Joyce-Shaikh, W. Blumenschein, T. Mcclanahan, J. O’Shea, D. Cua. Nature Immunology, 2009

1,081 citations recorded by the source corpus.

Interleukin 23 (IL-23) is required for autoimmune inflammation mediated by IL-17-producing helper T cells (TH-17 cells) and has been linked to many human immune disorders. Here we restricted deficiency in the IL-23 receptor to defined cell populations in vivo to investigate the requirement for IL-23 signaling in the development and function of TH-17 cells in autoimmunity, inflammation and infection. In the absence of IL-23, TH-17 development was stalled at the early activation stage. TH-17 cells failed to downregulate IL-2 and also failed to maintain IL-17 production or upregulate expression of the IL-7 receptor α-chain. These defects were associated with less proliferation; consequently, fewer effector TH-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues.

Subfields: Dermatology, Immunology

View Paper: https://www.semanticscholar.org/paper/70261effe386b75a0755a4da4a984bea5c6637e7

How researchers see this paper

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

In Dermatology

1. Y. Iwakura
2. H. Ishigame
3. C. Dong
4. D. Cua

In Immunology

1. W. E. Paul
2. Jinfang Zhu
3. R. Flavell
4. J. O’Shea
5. Alexander Y. Rudensky
6. C. Dong
7. Shizuo Akira
8. D. Artis

Citations in the corpus

• Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. (2009, background): “The absence of IL-23 signals greatly affects the numbers of Th17 cells and results in the failure to recruit or activate these cells (McGeachy et al., 2009; McGeachy and Cua, 2008), and, similarly, IL-17-producing gd T cells were compromised in the absence of IL-23.”
• Th17 cells promote cytotoxic T cell activation in tumor immunity (2009, background): “Th17 cells highly express IL-23R; IL-23 is required for the late stage of Th17 cell development and also functions to expand Th17 cells and promote their function (Langrish et al., 2005; McGeachy et al., 2009).”
• Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. (2010, background): “TGF-b and IL-6 are required for the differentiation of Th17 cells in mice, and IL-23 and IL-1 promote their differentiation (Iwakura et al., 2008; McGeachy et al., 2009).”
• RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation (2011, background): “In vivo , helper T cells unresponsive to IL-23 were impaired in their ability to invade the central nervous system (CNS), did not acquire encephalitogenic properties and were unable to secrete IL-17 (refs”
• Fate mapping of interleukin 17-producing T cells in inflammatory responses (2011, background): “T H 1-like effector profile in ex-T H 17 cells depends on IL-23 The importance of IL-23 signaling in the differentiation of T H 17 effector cells is well establishe”
• Structural activation of pro-inflammatory human cytokine IL-23 by cognate IL-23 receptor enables recruitment of the shared receptor IL-12Rβ1 (2017, background): “Indeed, IL-23R is required in vivo for effector Th17 cell responses (McGeachy et al., 2009), which are now closely associated with many autoimmune and chronic inflammatory disorders, including psoriasis, psoriatic arthritis, Crohn’s disease, rheumatoid arthritis, multiple sclerosis, inflammatory…”
• HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells (2011, background): “IL-23R is essential for terminal differentiation of TH17 cells (McGeachy et al., 2009), whereas Foxp3, the Treg cell master regulator, has been shown to antagonize ROR-t function and TH17 differentiation LDH- (lactate dehydrogenase), thus encompassing the entire spectrum of the glycolytic pathway.”
• IL-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability (2015, neutral): “d Neutralizing IL-17 results in increased gut permeability in a DSS injury model d gd T cells are themajor source of gut-protective IL-17 and are IL-23 independent d IL-17 regulates the cellular localization of the tight junction protein occludin d The data explain IBD exacerbation with anti-IL-17 b”
• Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10 dependent manner (2011, background): “IL-17A-Producing CD4 T Cells Express IL-10Ra CCR6, IL-23R, and IL-7R are known to be key receptors for the differentiation of pathogenic Th17 cells, which are expressed by the Th17 cell itself (Bettelli et al., 2007; Liu et al., 2010; McGeachy et al., 2009).”
• Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, background): “suggested to promote expansion of Th17 cells in peripheral tissues, and specifically in the colon (data not shown) (McGeachy et al., 2009).”
• CD4+ lymphoid tissue inducer cells promote innate immunity in the gut (2010, background): “, 2006), and it has been proposed that this defective immunity may be the result of impaired Th17 cell effector responses observed in the absence of IL-23 (McGeachy et al., 2009).”
• Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “IL-23 is important for full differentiation and maintenance of Th17 cells (36), although it is not involved in the initial differentiation stage due to lack of IL23R expression on naive CD4 T cells (8, 9, 37).”
• IL-6 in inflammation, autoimmunity and cancer (2020, background): “Consistently, IL-23R is essential for the terminal differentiation of T h 17 cells that are capable of inducing EAE in vivo (172).”