Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling

Chung, Yeonseok; Chang, Seon Hee; Martínez, Gustavo; Yang, Xuexian O.; Nurieva, Roza; Kang, Hong Soon; Ma, Li; Watowich, Stephanie S.; Jetten, Anton M.; Tian, Qiang; Dong, Chen

doi:10.1016/j.immuni.2009.02.007

Cited by 1,028 publications

(940 citation statements)

References 35 publications

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“…Thus, IL-23 favors IL-17A but does not affect IL-22 production and does not mediate the effect of TCDD. Pro-inflammatory IL-1 is critically needed for Th17 priming and expansion [5,7,8,20,35]. When purified CD4 1 T cells were activated in the presence of IL-1 receptor agonist (IL-1Ra), to block the membrane-bound IL-1a expressed by activated T cells, IL-17A production was practically abolished.…”

Section: Involvement Of Ahr In Upregulation Of Il-22 and Downregulatimentioning

confidence: 99%

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells

Ramirez¹,

Brembilla²,

Sorg³

et al. 2010

Eur J Immunol

158

139

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Ligands of the aryl hydrocarbon receptor (AHR), a transcription factor mediating the effects of dioxin, favor Th17 differentiation and exacerbate autoimmunity in mice. We investigated how AHR ligands affected human T-cell polarization. We found that the high affinity and stable AHR-ligand dioxin as well as the natural AHR-ligand 6-formylinolo [3,2-b] carbazole induced the downstream AHR-target cytochrome P450A1, and without affecting IFN-c, they enhanced IL-22 while simultaneously decreasing IL-17A production by CD4 1 T cells. The specific AHRinhibitor CH-223191 abolished these effects. Furthermore, blockade of IL-23 and IL-1, important for Th17 expansion, profoundly decreased IL-17A but not IL-22 production. AHR agonists reduced the expression of the Th17 master transcription factor retinoic acid-related orphan receptor C (RORC), without affecting T-bet, GATA-3 and Foxp3. They also decreased the expression of the IL-23 receptor. Importantly, AHR-ligation did not only decrease the number of Th17 cells but also primed naïve CD4 1 T cells to produce IL-22 without IL-17 and IFN-c. Furthermore, IL-22 single producers did not express CD161, which distinguished them from the CD161 1 Th17 cells. Hence, our data provide compelling evidence that AHR activation participates in shaping human CD4 1 T-cell polarization favoring the emergence of a distinct subset of IL-22-producing cells that are independent from the Th17 lineage. IntroductionLocal cytokine milieu during antigen presentation profoundly affects the differentiation program of CD4 1 T cells [1]. In the mouse, TGF-b, in the presence of IL-6 and pro-inflammatory cytokines, favors the emergence of Th17 cells that produce IL-17 and express the master transcription factor retinoic acid-related orphan receptor (ROR)gt [2][3][4][5][6]. Th17 cells are expanded and terminally differentiated in the presence of . Human Th17 cells may be generated in the presence of IL-1 and IL-23; IL-1 and IL-6; or . Th17 cells express CCR6 and 2450produce the CCR6-ligand CCL20, thereby amplifying Th17 cell recruitment at sites of inflammation [11]. IL-22, a member of the IL-10-family, is produced by Th17 cells, and to some extent by Th1 cells, NKT cells, NK cells and lymphoid tissue inducer-like cells [12]. IL-22 signals via a receptor consisting of IL-22R and IL-10R2 subunits [11]. Cells of hemapoietic origin do not express IL-22R; instead, IL-2R is highly expressed by epithelial cells of the gastrointestinal tract and the skin. In the mouse, IL-23 was shown to drive preferential expansion of cells that co-express IL-22 and IL-17, that may synergize to augment the expression of genes involved in defense against microbial pathogens [13,14]. However, several mouse models of infection and autoimmunity suggested distinct roles for .In addition to cytokines, other mediators may impact CD4 1 T-cell differentiation. We and others have shown that prostaglandin E2 (PGE2) favors human Th17 expansion [20][21][22]. Furthermore, ligands of the aryl hydrocarbon receptor (AHR) exert a role. AHR is a...

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Section: Involvement Of Ahr In Upregulation Of Il-22 and Downregulatimentioning

confidence: 99%

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells

Ramirez¹,

Brembilla²,

Sorg³

et al. 2010

Eur J Immunol

158

139

View full text Add to dashboard Cite

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“…Because IL-1 and IL-6 promote the conversion of FoxP3 þ Treg cells to IL-17-producing FoxP3 þ cells, we concentrated on these subsets (Xu et al, 2007;Zhou et al, 2008;Chung et al, 2009). We quantified Treg cells in a panel of LNs and spleen from naive and 3 week TPA-treated wildtype and Cd200 À/À mice, thus before the onset of first macroscopic papillomas (Figure 4a).…”

Section: Cd200-cd200r Signaling In Tumorigenesismentioning

confidence: 99%

“…Tolerance to exogenous antigens can be conferred by transfer of Treg cells from tolerized animals into naive recipients (Unger et al, 2003b). However, in inflammatory conditions Treg cells can change their phenotype and start to produce interleukin (IL)-17, mimicking Th17 cells (Koenen et al, 2008;Zhou et al, 2008;Baban et al, 2009;Chung et al, 2009;Murphy and Stockinger, 2010). Th17 cells specifically express the transcription factor RORg and are mostly known for their instrumental role in the development of autoimmune diseases (Fouser et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

et al. 2011

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“…79 IL-1b plays an important role in activating and sustaining the Th17-mediated response, especially in humans. [107][108][109][110] Considering the central role of Th17 cells in autoimmune diseases including rheumatoid arthritis (RA) and psoriasis, mutations in inflammasome-encoding genes may result in a broad spectrum of Th17 cell-mediated autoimmune disorders, through deregulation of IL-1b secretion. 107,[111][112][113][114][115][116] Genetic variants in several inflammatory genes, including NLRP3, are associated with two forms of autoimmune arthritis: juvenile idiopathic arthritis and RA, characterized by Th17 cells.…”

Section: Adaptive Immunity-mediated Diseasesmentioning

confidence: 99%

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

2011

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Nucleotide-binding oligomerization domain (NOD)-containing protein-like receptors (NLRs) are a recently discovered class of innate immune receptors that play a crucial role in initiating the inflammatory response following pathogen recognition. Some NLRs form the framework for cytosolic platforms called inflammasomes, which orchestrate the early inflammatory process via IL-1b activation. Mutations and polymorphisms in NLR-coding genes or in genetic loci encoding inflammasome-related proteins correlate with a variety of autoinflammatory diseases. Moreover, the activity of certain inflammasomes is associated with susceptibility to infections as well as autoimmunity and tumorigenesis. In this review, we will discuss how identifying the genetic characteristics of inflammasomes is assisting our understanding of both autoinflammatory diseases as well as other immune system-driven disorders.

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Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling

Cited by 1,028 publications

References 35 publications

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells

CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

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