Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells

Duhen, Thomas; Geiger, Rebekka; Jarrossay, David; Lanzavecchia, Antonio; Sallusto, Federica

doi:10.1038/ni.1767

Cited by 944 publications

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“…These data are at variance with the reduction of IL-22 reported in CD4 1 memory T cells in which RORC was silenced [31], but in agreement with the finding that Th22 clones express lower RORC levels than Th17 clones [32,33] and with the fact that lentivirus-induced expression of RORgt in human naïve T cells results in IL-17 without IL-22 production [5]. In this respect, it is important to note that whole genome transcritpome analysis of T-cell clones with preferential IL-22 production pointed to the preferential expression of BNC2 and FOXO4 transcription factors when compared to Th1, Th2 and Th17 cell clones [33].…”

Section: Discussionsupporting

confidence: 88%

“…Human lymphocytes may, however, behave differently and in a recent report AHR agonists appear to favor IL-22 but not IL-17 production [31]. These cells have been named Th22 cells and are thought to be involved in skin immunosurveillance and skin immunopathology [32,33].In the current study, we investigated the effect of synthetic and natural AHR ligands on the production of the human T helper signature-cytokines IL-17A, IFN-g and IL-22. We found that AHR ligands decrease Th17 polarization and favor the differentiation of a subset of CD4 1 T cells that produce IL-22 independently from IL-17A or IFN-g.…”

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confidence: 94%

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confidence: 99%

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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

163

141

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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: Discussionsupporting

confidence: 88%

mentioning

confidence: 94%

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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

163

141

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“…Moreover, after bleomycin administration, the majority of IL-22-expressing cells in the lung coexpresses IL-17A and promotes inflammation [44]. In contrast, subsets of gut-resident NK cells and skin-resident CD4 1 T cells were reported to express IL-22 but do not coexpress IL-17 [17,[45][46][47] and appear to contribute to a constitutive tissue-protective role in mouse models of inflammation of the intestine or skin. Collectively, these reports suggest that the production of IL-22 in the absence of IL-17 is important in promoting tissueprotective responses.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the development of acute hepatitis by IL‐23 through IL‐22 and IL‐17 production

Morishima

Mizoguchi

et al. 2011

Eur J Immunol

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IL-23 plays a critical role in the expansion of highly proinflammatory Th17 cells secreting . Recently, we demonstrated that Notch signaling drives IL-22 secretion through the aryl hydrocarbon receptor (AHR) and plays a protective role in Con A-induced hepatitis. In this study, we investigated the role of IL-23 in hepatitis using IL-23p19-and IL-17-deficient mice. In WT mice, the injection of Con A induced the upregulation of various cytokines, which included IL-23, IL-22, IL-17, IFN-c and TNF-a. In IL-23p19-deficient mice, exacerbated hepatitis was observed and serum IL-22 and IL-17 levels were greatly reduced, whereas in IL-17-deficient mice, ameliorated hepatitis was observed. The injection of exogenous IL-22 protected p19-deficient mice from hepatitis, whereas the injection of exogenous IL-23 significantly increased the serum levels of not only IL-22 but also IL-17, and less effectively protected against hepatitis in IL-17-dependent and -independent manners. Finally, it was revealed that STAT3, STAT4 and Notch contributed to the production of both the cytokines, and that the AHR was important only for IL-22 production in response to Con A and IL-23 in liver mononuclear cells. These results suggest that IL-23 plays a protective role in hepatitis through IL-22 production and also a pathological role via IL-17-dependent and -independent mechanisms.Key words: Hepatitis . IL-17 . IL-22 . IL-23Supporting Information available online Introduction IL-23 is a heterodimeric cytokine which belongs to the IL-6/IL-12 family and plays a key role in autoimmune and inflammatory disorders [1]. IL-23 acts on memory-type cells [2] and induces the production of . Moreover, IL-23 is an essential factor in the survival and expansion of Th17 cells [5], which produce cytokines including IL-17, IL-17F, . p19-deficient mice are highly resistant to the development of experimental allergic encephalomyelitis (EAE) [7], and it has been shown that the IL-23-dependent production of IL-17, but not , is important for the pathogenesis of autoimmune 2828diseases such as EAE [9]. Recent studies have also revealed that the IL-23-dependent production of IL-22, but not IL-17, plays a critical role in protection against subsequent infection. In infection with an attenuated strain of Salmonella enterica serovar Enteritidis, p19-deficient mice showed reduced survival and exacerbated liver necrosis only in the absence of IL-12 in an IL-17-independent manner [10]. In peroral infection with Toxoplasma gondii, which leads to the development of small intestine inflammation, the IL-23-dependent upregulation of IL-22 is essential for the development of ileitis; on the other hand, IL-17 is downregulated and dispensable [11].IL-22 is a member of the IL-10 cytokine family and plays important roles in inflammation, immune surveillance and tissue homeostasis [12][13][14][15] [10,25,26].Recently, we demonstrated that Notch, which is an evolutionally conserved molecule that controls cell fate decision in a variety of cells [27,28], drives IL-22 secretion by stimu...

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“…L'IL-22 était considérée comme étant la caractéristique des lymphocytes Th17, jusqu'à ce que deux études [49,50] Concernant les inhibiteurs de la signalisation, un essai de phase III évaluant l'efficacité dans le psoriasis en plaques modéré à sévère du tofacitinib, un inhibiteur de JAK (Janus kinase) 1 et JAK3 (des kinases impliquées dans les voies JAK/STAT de signalisation en aval de nombreux récepteurs de cytokines), a montré un effet équivalent de la molécule par rapport au récepteur soluble au TNF-α, l'étanercept, et sa supériorité par rapport au placebo [48].…”

Section: Perspectives : Inhibition De L'interleukine 22unclassified

Immunopathologie du psoriasis

et al. 2016

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> Le psoriasis est une maladie inflammatoire fréquente atteignant essentiellement la peau et parfois les articulations. Cette maladie chronique met rarement en jeu le pronostic vital mais altère significativement la qualité de vie. Le psoriasis est caractérisé, dans sa forme la plus fréquente, par des plaques érythémato-squameuses bien limitées associées à une prolifération exagérée des kératinocytes de l'épiderme, une inflammation et une hypervascularisation du derme superficiel. L'implication des lymphocytes T CD4 de type Th1 a été suspectée initialement. Plus récemment, la découverte du rôle prépondérant des lymphocytes T CD4 de type Th17 dans la maladie a conduit au développement d'inhibiteurs spécifiques de cette voie, tels que les anticorps anti-IL(interleukine)-23 (cytokine favorisant la différenciation des lymphocytes en Th17), anti-IL-17, anti-IL-17RA (récepteur de l'IL-17) et IL-22 (cytokine produite notamment par les lymphocytes Th17). < Structure de la peau humaine normaleLa peau humaine (Figure 1) est constituée de trois couches qui sont, de la profondeur à la superficie, l'hypoderme, le derme et l'épiderme. L'hypoderme est majoritairement constitué des adipocytes qui sont des cellules chargées de lipides. Le derme contient un tissu interstitiel formé de collagène, des vaisseaux sanguins, des annexes piloséba-cées et des cellules du système immunitaire. L'épiderme est constitué de kératinocytes organisés en quatre couches. La plus profonde, la couche basale (stratum basale), est au contact de la membrane basale qui sépare l'épiderme du derme superficiel. Elle est constituée des kératinocytes basaux qui prolifèrent et se différencient en kératinocytes des couches supérieures, c'est-à-dire couche épineuse (stratum spinosum ou corps muqueux de Malpighi), couche granuleuse (stratum granulosum), et couche cornée (stratum corneum) en superficie. Les kératinocytes présents au niveau de la couche cornée (les 1 Inserm U976, laboratoire oncodermatologie, immunologie et cellules souches cutanées, hôpi-tal Saint-Louis,

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Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells

Cited by 944 publications

References 50 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

Regulation of the development of acute hepatitis by IL‐23 through IL‐22 and IL‐17 production

Immunopathologie du psoriasis

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