Role of Co-stimulatory Molecules in T Helper Cell Differentiation

Schorer, Michelle; Kuchroo, Vijay K.; Joller, Nicole

doi:10.1007/978-981-32-9717-3_6

Cited by 23 publications

(10 citation statements)

References 167 publications

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“…Potent Tfh might play a crucial role in IgG4 class switching [ 35 ]; therefore, the elevated levels of sTIM-3 may affect the Tfh functions by interfering with the Gal-9/TIM-3 co-inhibitory checkpoint systems. These co-inhibitory checkpoint pathways may alter the interaction between Tfh cells and plasmablasts [ 36 ] in the immunopathology of IgG4-RD and its expanding organ involvement. Given the multi-organ nature of IgG4-RD, the predictors for particular organ involvements would be valuable for clinical application and research of IgG4-RD.…”

Section: Discussionmentioning

confidence: 99%

Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

et al. 2021

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Background Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. Methods Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD. Results In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. Conclusion Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

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Section: Discussionmentioning

confidence: 99%

Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

et al. 2021

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“…In chronic inflammatory diseases, T lymphocytes control and regulate the host response by taking advantage of their memory properties and high cytokine-producing capacities ( 18 ). T lymphocytes are categorized into a variety of T helper (Th) subgroups, including T h 1, T h 2, T h 17, and regulatory T cells (Treg), showing anti-inflammatory or pro-inflammatory properties ( 19 ) among these subgroups.…”

Section: Introductionmentioning

confidence: 99%

Resolvin E1 Regulates Th17 Function and T Cell Activation

et al. 2021

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Resolvin E1 (RvE1) is a specialized pro-resolving lipid mediator derived from eicosapentaenoic acid and plays a critical role in resolving inflammation and tissue homeostasis. Th17 cells are a distinct group of T helper (Th) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases via the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the Th17-induced progression of inflammation and tissue destruction. In this study, we hypothesized that the RvE1 would restore homeostatic balance and inflammation by targeting the Th17 function. We designed three experiments to investigate the impact of RvE1 on different phases of Th17 response and the potential role of DCs: First CD4+ T cells were induced by IL-6/TGFβ to measure the effect of RvE1 on Th17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated Th17 differentiation in a co-culture model. Third, we measured the effect of RvE1 on DC maturation. RvE1 blocked the CD25, CCR6 and IL-17 expression; IL-17, IL-21, IL-10, and IL-2 production, suggesting inhibition of T cell activation, Th17 stimulation and chemoattraction. RvE1 also suppressed the activation of DCs by limiting their pro-inflammatory cytokine production. Our findings collectively demonstrated that the RvE1 targeted the Th17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.

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“…After being stimulated by antigens and cytokines, CD4+ T cells acquire the ability to differentiate into different cell subtypes with specific effects. These cell subtypes adjust the immune system to exert corresponding immune effects according to different pathogens [ 9 ]. Th1 cells secrete mainly IL-2, IFN- γ , and TNF- α , regulating the cell-mediated immune response [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Directs T Helper Cells toward Th1 Cell Differentiation via the STAT1-T-Bet Pathway

Lei

Liu

Xie

et al. 2021

BioMed Research International

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Dexmedetomidine is an α2 adrenergic receptor agonist that has been reported to modulate the polarization of CD4+ T cells. However, the underlying mechanisms by which dexmedetomidine induces T-helper 1 (Th1) cell differentiation remain poorly understood. The aim of this study was to explore the potential mechanisms through which dexmedetomidine can induce Th1 cell differentiation. Purified CD4+ T cells were stimulated with anti-CD3/anti-CD28 and then treated with dexmedetomidine. Flow cytometry analysis was adopted to measure the concentration of Th1 cells. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR) were performed to detect protein levels and mRNA expression, respectively, of IFN-γ and IL-4. Western blotting was used to determine the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and T-bet expression. The Th1 cell subset and IFN-γ levels were elevated in the dexmedetomidine-induced CD4+ T cells. Dexmedetomidine enhanced the phosphorylation of STAT1 and the expression of T-bet in the CD4+ T cells. Atipamezole (an α2 adrenergic antagonist) and fludarabine (a STAT1 inhibitor) reversed the dexmedetomidine-induced Th1 cell differentiation. These results suggested that dexmedetomidine induced Th1 cell differentiation via the STAT1-T-bet signaling pathway.

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Role of Co-stimulatory Molecules in T Helper Cell Differentiation

Cited by 23 publications

References 167 publications

Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD)

Resolvin E1 Regulates Th17 Function and T Cell Activation

Dexmedetomidine Directs T Helper Cells toward Th1 Cell Differentiation via the STAT1-T-Bet Pathway

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