scholarly journals Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion

2009 ◽  
Vol 15 (6) ◽  
pp. 633-640 ◽  
Author(s):  
Chengcan Yao ◽  
Daiji Sakata ◽  
Yoshiyasu Esaki ◽  
Youxian Li ◽  
Toshiyuki Matsuoka ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Prostaglandin E2 ◽  
Cell Expansion ◽  
Th17 Cell ◽  
Th1 Cell ◽  
Immune Inflammation

Prostaglandin E Receptor Subtypes EP2 and EP4 Promote TH1 Cell Differentiation and TH17 Cell Expansion Through Different Signaling Modules

2009 ◽  
Vol 58 (S2) ◽  
pp. S244-S248 ◽  
Author(s):  
Daiji Sakata ◽  
Chengcan Yao ◽  
Yoshiyasu Esaki ◽  
Youxian Li ◽  
Toshiyuki Matsuoka ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Expansion ◽  
Th17 Cell ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Th1 Cell ◽  
Signaling Modules

scholarly journals Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells’ Differentiation and Function in Induction of Colitis

2019 ◽  
Vol 25 (9) ◽  
pp. 1450-1461 ◽  
Author(s):  
Liang Chen ◽  
Mingming Sun ◽  
Wei Wu ◽  
Wenjing Yang ◽  
Xiangsheng Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Gut Microbiota ◽  
Th17 Cell ◽  
Cell Development ◽  
Cell Polarization ◽  
T Cell Differentiation ◽  
Th1 Cell ◽  
And Function

Abstract Background How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated. Methods CBir1, an immunodominant microbiota antigen, transgenic T cells were treated with butyrate under various T-cell polarization conditions to investigate butyrate regulation of T-cell differentiation and the mechanism involved. Transfer of butyrate-treated CBir T cells into Rag1-/- mice was performed to study the in vivo role of such T cells in inducing colitis. Results Although butyrate promoted Th1 cell development by promoting IFN-γ and T-bet expression, it inhibited Th17 cell development by suppressing IL-17, Rorα, and Rorγt expression. Interestingly, butyrate upregulated IL-10 production in T cells both under Th1 and Th17 cell conditions. Furthermore, butyrate induced T-cell B-lymphocyte-induced maturation protein 1 (Blimp1) expression, and deficiency of Blimp1 in T cells impaired the butyrate upregulation of IL-10 production, indicating that butyrate promotes T-cell IL-10 production at least partially through Blimp1. Rag1-/- mice transferred with butyrate-treated T cells demonstrated less severe colitis, compared with transfer of untreated T cells, and administration of anti-IL-10R antibody exacerbated colitis development in Rag-/- mice that had received butyrate-treated T cells. Mechanistically, the effects of butyrate on the development of Th1 cells was through inhibition of histone deacetylase but was independent of GPR43. Conclusions These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease.

scholarly journals Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation

2021 ◽  
Vol 22 (14) ◽  
pp. 7535
Author(s):  
Hye-Soo Park ◽  
Seunga Choi ◽  
Yong-Woo Back ◽  
Kang-In Lee ◽  
Han-Gyu Choi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Differentiation ◽  
Prostaglandin E2 ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Bacterial Load ◽  
Cell Responses ◽  
Ep4 Receptor ◽  
Th17 Cell Differentiation

Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Currently, there are no reports on the mycobacterial components that regulate PGE2 production. Previously, we have reported that RpfE-treated dendritic cells (DCs) effectively expanded the Th1 and Th17 cell responses simultaneously; however, the mechanism underlying Th1 and Th17 cell differentiation is unclear. Here, we show that PGE2 produced by RpfE-activated DCs via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor. Furthermore, mice administered intranasally with PGE2 displayed RpfE-induced antigen-specific Th1 and Th17 responses with a significant reduction in bacterial load in the lungs. Furthermore, the addition of optimal PGE2 amount to IL-2-IL-6-IL-23p19-IL-1β was essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity. These results suggest that RpfE-matured DCs produce PGE2 that induces Th1 and Th17 cell differentiation with potent anti-mycobacterial activity.

scholarly journals Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling

2009 ◽  
Vol 184 (6) ◽  
pp. i16-i16
Author(s):  
Katia Boniface ◽  
Kristian S. Bak-Jensen ◽  
Ying Li ◽  
Wendy M. Blumenschein ◽  
Mandy J. McGeachy ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cyclic Amp ◽  
Prostaglandin E2 ◽  
Th17 Cell ◽  
Receptor Signaling ◽  
Ep4 Receptor ◽  
Th17 Cell Differentiation ◽  
And Function

scholarly journals Mycobacterium Tuberculosis RpfE-induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation

2021 ◽  
Author(s):  
Hye-Soo Park ◽  
Seunga Choi ◽  
Yong Woo Back ◽  
Kang-In Lee ◽  
Han-Gyu Choi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Differentiation ◽  
Prostaglandin E2 ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Bacterial Load ◽  
Cell Responses ◽  
Ep4 Receptor ◽  
Th17 Cell Differentiation

Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Currently, there are no reports on the mycobacterial components that regulate PGE2 production. Previously, we have reported that RpfE-treated dendritic cells (DCs) effectively expanded the Th1 and Th17 cell responses simultaneously; however, the mechanism underlying Th1 and Th17 cell differentiation is unclear. Here, we show that PGE2 produced by RpfE-activated DCs via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor. Furthermore, mice administered intranasally with PGE2 displayed RpfE-induced antigen-specific Th1 and Th17 responses with a significant reduction in bacterial load in the lungs. Furthermore, the addition of optimal PGE2 amount to IL-2-IL-6-IL-23p19-IL-1β was essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity. These results suggest that RpfE-matured DCs produce PGE2 that induces Th1 and Th17 cell differentiation with potent anti-mycobacterial activity.

scholarly journals The CTRP3-AdipoR2 Axis Regulates the Development of Experimental Autoimmune Encephalomyelitis by Suppressing Th17 Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Masanori A. Murayama ◽  
Hsi-Hua Chi ◽  
Mako Matsuoka ◽  
Takahiro Ono ◽  
Yoichiro Iwakura
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cell ◽  
Autoimmune Encephalomyelitis ◽  
Th1 Cell ◽  
Th17 Cell Differentiation ◽  
Good Target ◽  
Complement C1q ◽  
Experimental Autoimmune

C1q/TNF-related proteins (CTRP) including CTRP3 are a group of secreted proteins which have a complement C1q-like domain in common, and play versatile roles in lipid metabolism, inflammation, tumor metastasis and bone metabolism. Previously, we showed that the expression of C1qtnf3, encoding CTRP3, is highly augmented in joints of autoimmune arthritis models and CTRP3-deficiency exacerbates collagen-induced arthritis in mice. However, the mechanisms how CTRP3-deficiency exacerbates arthritis still remain to be elucidated. In this study, we showed that CTRP3 was highly expressed in Th17 cell, a key player for the development of autoimmune diseases, and Th17 cell differentiation was augmented in C1qtnf3–/– mice. Th17 cell differentiation, but not Th1 cell differentiation, was suppressed by CTRP3 and this suppression was abolished by the treatment with a receptor antagonist against AdipoR2, but not AdipoR1, associated with suppression of Rorc and Stat3 expression. Furthermore, AdipoR1 and AdipoR2 agonist, AdipoRon suppressed Th17 cell differentiation via AdipoR2, but not AdipoR1. The development of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis was enhanced in C1qtnf3–/– mice associated with increase of Th17 cell population. CTRP3 inhibited MOG-induced IL-17 production from T cells by affecting both T cells and dendritic cells. These results show that CTRP3 is an endogenous regulator of Th17 differentiation, suggesting that the CTRP3-AdipoR2 axis is a good target for the treatment of Th17 cell-mediated diseases.

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