Fas signaling-mediated TH9 cell differentiation favors bowel inflammation and antitumor functions

Shen, Yingying; Song, Zhengbo; Lu, Xinliang; Ma, Zeyu; Lu, Chaojie; Zhang, Bei; Chen, Yinghu; Meng, Di; Apétoh, Lionel; Xu, Li; Guo, Jufeng; Miao, Ying; Zhang, Gensheng; Yang, Diya; Cai, Zhijian; Wang, Jianli

doi:10.1038/s41467-019-10889-4

Cited by 38 publications

(24 citation statements)

References 57 publications

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“…Previous studies showed Th17 cells have moderate antitumor immunity in the B16-OVA melanoma model 15 . However, Th9 cells have been shown to have potent antitumor activity in this model 15,[53][54][55][56] . In the OVA sensitization model ( Fig.…”

Section: Stat6 -/-mentioning

confidence: 88%

STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

Wang

Panangipalli

et al. 2020

Nat Commun

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T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.

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Section: Stat6 -/-mentioning

confidence: 88%

STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

Wang

Panangipalli

et al. 2020

Nat Commun

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“…FAS encodes a protein containing a death domain and plays a central role in the physiological regulation of programmed cell death. FAS has also been implicated in the pathogenesis of various malignancies and immune diseases [23]. The interaction of this receptor with its ligand leads to the formation of a death-inducing signaling complex that triggers a downstream caspase cascade, leading to apoptosis [24].…”

Section: Discussionmentioning

confidence: 99%

Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-dependent manner in swine neutrophils

Huang

Jiang

Yang

et al. 2020

Vet Res

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Neutrophils are the first barriers for resisting the invasion, proliferation, and damage caused by Salmonella Typhimurium. However, the mechanisms that control this resistance are not completely understood. In this study, we established an in vitro Salmonella infection model in porcine neutrophils, and analyzed the cellular transcriptome by deep sequencing and flow cytometry. The results showed that ribosomal gene transcription was inhibited, and two of these genes, RPL39 and RPL9, were related to TRP53 activation. Furthermore, several important innate immunity genes were also inhibited. Knock-down of RPL39 and RPL9 by siRNA caused an approximate fourfold up-regulation of TRP53. Knock-down of RPL39 and RPL9 also resulted in a significant down-regulation of IFNG and TNF, indicating an inhibition of the innate immune response. Silencing of RPL39 and RPL9 also resulted in the up-regulation of FAS, RB1, CASP6, and GADD45A, which play roles in cell cycle arrest and apoptosis. Neutrophils were either first treated with RPL39 siRNA, RPL9 siRNA, TRP53 activator, or TRP53 inhibitor, and then infected with Salmonella. Knock-down of RPL39 and RPL9, or treatment with TRP53 activator, can increase the intracellular proliferation of Salmonella in neutrophils. We speculate that much of the Salmonella virulence can be attributed to the enhancement of cell cycle arrest and the inhibition of the innate immune response, which allows the bacteria to successfully proliferate intracellularly.

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“…In Lewis lung carcinoma OVA-bearing mice, Fas costimulatory signaling could promote Th9 cell differentiation and IL-9 production, as well as IFN- γ producing CD8 + T cell generation to enhance antitumor immunity. Mechanistically, Fas signaling activated PKC β , which induced activation of NF- κ B and p38 MAPK to promote Th9 cell differentiation [ 200 ]. Moreover, IL-2 and agonistic CD40 antibody ( α CD40) treatment induced Fas-mediated elimination of Treg cells in the renal adenocarcinoma (Renca) tumor-bearing mice.…”

Section: Molecular Mechanisms That Influence the Balance Between Tmentioning

confidence: 99%

Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

Huang

Dong

2021

Journal of Immunology Research

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CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

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Fas signaling-mediated TH9 cell differentiation favors bowel inflammation and antitumor functions

Cited by 38 publications

References 57 publications

STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

Salmonella enterica serovar Typhimurium inhibits the innate immune response and promotes apoptosis in a ribosomal/TRP53-dependent manner in swine neutrophils

Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

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