Murine NKT cells produce Th17 cytokine interleukin-22

Goto, Megumi; Murakawa, Masao; Kadoshima-Yamaoka, Kumiko; Tanaka, Yoshitaka; Nagahira, Kazuhiro; Fukuda, Yoshiaki; Nishimura, Takashi

doi:10.1016/j.cellimm.2008.10.002

Cited by 93 publications

(65 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to CD4 ϩ T cells, other cell populations have recently been shown to produce IL-17 by either direct or indirect stimulation by microbes or their stimuli during infection. CD8 ϩ cytotoxic T cells, ␥␦ T cells, NK cells, NKT cells, and LTi cells are among the populations that are significant producers of IL-17A upon stimulation (16,27,29,54,56,58,68,75). To confirm our in vitro findings with CD4 ϩ T cells and further determine which of the above populations contribute to IL-17A production in vivo during S. Typhimurium infection, we employed a multicolor flow cytometry approach.…”

Section: Characterization Of the Curli Mutantmentioning

confidence: 91%

Microbial Amyloids Induce Interleukin 17A (IL-17A) and IL-22 Responses via Toll-Like Receptor 2 Activation in the Intestinal Mucosa

et al. 2012

View full text Add to dashboard Cite

The Toll-like receptor 2 (TLR2)/TLR1 receptor complex responds to amyloid fibrils, a common component of biofilm material produced by members of the phyla Firmicutes, Bacteroidetes, and Proteobacteria. To determine whether this TLR2/TLR1 ligand stimulates inflammatory responses when bacteria enter intestinal tissue, we investigated whether expression of curli amyloid fibrils by the invasive enteric pathogen Salmonella enterica serotype Typhimurium contributes to T helper 1 and T helper 17 responses by measuring cytokine production in the mouse colitis model. A csgBA mutant, deficient in curli production, elicited decreased expression of interleukin 17A (IL-17A) and IL-22 in the cecal mucosa compared to the S. Typhimurium wild type. In TLR2-deficient mice, IL-17A and IL-22 expression was blunted during S. Typhimurium infection, suggesting that activation of the TLR2 signaling pathway contributes to the expression of these cytokines. T cells incubated with supernatants from bone marrow-derived dendritic cells (BMDCs) treated with curli fibrils released IL-17A in a TLR2-dependent manner in vitro. Lower levels of IL-6 and IL-23 production were detected in the supernatants of the TLR2-deficient BMDCs treated with curli fibrils. Consistent with this, three distinct T-cell populations-CD4؉ T helper cells, cytotoxic CD8 ؉ T cells, and ␥␦ T cells-produced IL-17A in response to curli fibrils in the intestinal mucosa during S. Typhimurium infection. Notably, decreased IL-6 expression by the dendritic cells and decreased IL-23 expression by the dendritic cells and macrophages were observed in the cecal mucosa of mice infected with the curli mutant. We conclude that TLR2 recognition of bacterial amyloid fibrils in the intestinal mucosa represents a novel mechanism of immunoregulation, which contributes to the generation of inflammatory responses, including production of IL-17A and IL-22, in response to bacterial entry into the intestinal mucosa.

show abstract

Section: Characterization Of the Curli Mutantmentioning

confidence: 91%

Microbial Amyloids Induce Interleukin 17A (IL-17A) and IL-22 Responses via Toll-Like Receptor 2 Activation in the Intestinal Mucosa

et al. 2012

View full text Add to dashboard Cite

show abstract

“…IL-22 was first reported to be associated with Th1 cells but was subsequently shown to be secreted by Th17 cells, gdT cells, NKT cells, NK cells, CD11c 1 myeloid cells and lymphoid tissue inducer-like cells [16][17][18][19]. The in vitro differentiation of Th17 cells produces a population of cells with a single expression of IL-17 and IL-22 and the coexpression of IL-17 and IL-22 [16].…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…Activation of the IL-22 receptor leads to STAT 1,3,5 signalling followed by nuclear factor kb, MAPK and PI3K-AKT-mTOR pathway activation [160]. Although IL-22 is produced by immune cells, IL-22R1 is selectively expressed on non-immune cells especially smooth muscle cells, thymic epithelial cells, liver stellate cells and myofibroblasts of colonic submucosa [164][165][166].…”

Section: Other Interleukinsmentioning

confidence: 99%

“…It is mainly secreted by helper T lymphocytes, CD8 + lymphocytes, innate lymphoid cells and NK cells, but during inflammatory process it can be induced by both lymphoid and myeloid cells such as dendritic cells, macrophages and neutrophils. These myeloid sources of IL-22 are suggested as the main source of the cytokine during pathological and regenerative processes in non-hematopoietic tissues such as intestines, lung, kidney, and liver [159][160][161][162][163].…”

Section: Other Interleukinsmentioning

confidence: 99%