scholarly journals Regulatory T cells induce polarization of pro-repair macrophages by secreting sFGL2 into the endometriotic milieu

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xin-Xin Hou ◽  
Xiao-Qiu Wang ◽  
Wen-Jie Zhou ◽  
Da-Jin Li
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Signaling Pathway ◽  
Peritoneal Fluid ◽  
Macrophage Polarization ◽  
Induce Polarization ◽  
Highly Active ◽  
Stat3 Signaling ◽  
Macrophages Polarization ◽  
Stat3 Signaling Pathway

AbstractAn increased number of highly active regulatory T cells (Tregs) and macrophages has been found in peritoneal fluid from women with endometriosis. Here, we show that the level of Tregs-derived soluble fibrinogen-like protein 2 (sFGL2) increases in the peritoneal fluid of women with endometriosis. Higher expression of FGL2 and its receptor CD32B is observed in eutopic endometrium and ectopic tissues. The production of sFGL2 in Tregs may be enhanced by several cytokines. sFGL2 selectively induces pro-repair macrophage polarization mainly through the activation of the SHP2-ERK1/2-STAT3 signaling pathway, and the suppression of the NF-κB signaling pathway. Furthermore, sFGL2 induces a much higher level of metallothionein (MT) expression that in turn facilitates pro-repair macrophages polarization. sFGL2-induced pro-repair macrophages promote Th2 and Tregs differentiation, creating a positive feedback loop. These findings suggest that sFGL2 secreted by Tregs skews macrophages toward a pro-repair phenotype via SHP2-ERK1/2-STAT3 signaling pathway, which is involved in the progression of endometriosis.

scholarly journals Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling

2021 ◽  
Author(s):  
Shasha Liu ◽  
Chaoqi Zhang ◽  
Boqiao Wang ◽  
Huanyu Zhang ◽  
Guohui Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Growth ◽  
Xenograft Model ◽  
Malignant Growth ◽  
Cancer Stemness ◽  
The Core ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tumorigenic Potential

AbstractGlioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF-β secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-β acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB–IL6–STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential. Furthermore, Tregs promoted glioma tumor growth, and this effect could be abrogated with blockade of IL6 receptor by tocilizumab which also demonstrated certain level of therapeutic efficacy in xenograft model. Additionally, expression levels of CD133, IL6 and TGF-β were found to serve as prognosis markers of glioma patients. Collectively, our findings reveal a new immune-associated mechanism underlying Tregs-induced GSCs. Moreover, efforts to target this network may be an effective strategy for treating glioma.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway

2019 ◽  
Vol 17 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Ling-Na KONG ◽  
Xiang LIN ◽  
Cheng HUANG ◽  
Tao-Tao MA ◽  
Xiao-Ming MENG ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Macrophage Polarization ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling

2020 ◽  
Author(s):  
Shasha Liu ◽  
Chaoqi Zhang ◽  
Boqiao Wang ◽  
Huanyu Zhang ◽  
Congcong Li ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Noncancerous Tissue ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tumorigenic Potential ◽  
Sphere Formation

Abstract Background: Glioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and the tumor microenvironment (TME). The aim of this study was to examine how regulatory T cells (Tregs) increase the stemness and tumorigenic potential of glioma cells.Methods: Tumor and peripheral blood samples were collected during surgery from 86 patients with glioma, and 75 samples of adjacent noncancerous tissue were collected, and Regulatory T cells (Tregs) were extracted from blood. Cytological and histochemical analyses were conducted to examine the mechanisms of Treg action on cancer cells. A mouse glioma model was used.Results: Intense infiltration by Tregs facilitated the qualities of GSCs through TGF-β secretion, which helped to coordinate tumor growth. Mechanistic investigations indicated that TGF-b acted on cancer cells to induce expression of the core cancer stem cell-related genes ( CD133, SOX2, NESTIN, MUSASHI1, and ALDH1A ) and to induce sphere formation via the NF-κB–IL6–STAT3 signaling pathway, resulting in increased cancer stemness and tumorigenic potential. Tregs promoted glioma tumor growth, and this effect was abrogated by blockade of the IL6 receptor by tocilizumab, which also demonstrated some therapeutic efficacy in a xenograft model. Expression levels of CD133, IL6 and TGF-β were found to serve as prognostic markers for glioma.Conclusions: Our findings reveal a new immune-associated mechanism underlying Treg-induced GSCs. Efforts to target this network may provide an effective strategy for treating glioma.

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