Pathogenic Roles of T Cells in Autoimmunity

Editorial

03 April 2024

Editorial: Pathogenic roles of T cells in autoimmunity

Jinfang Xia

Jifeng Tang

Qiong Fu

and

Jinpiao Lin

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Editors

Jinpiao Lin

Tongren Hospital, School of Medicine, Shanghai Jiao Tong University

Huimin Zhang

Stanford University

QIong Fu

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Impact

Oestrogen deficiency activates T cells to secrete a large number of Th17 cells and a smaller number of Treg cells, in which Th17 cells and the cytokines they secrete play a pro-inflammatory and pro-OC generation role, and Treg cells and the related cytokines they secrete play an anti-inflammatory and anti-OC generation role. However, the pro-inflammatory and pro-OC generation of Th17 cells far exceeded the anti-inflammatory and anti-bone resorption effects of Treg cells, which made the inflammatory response and bone resorption far greater than bone formation, leading to the development of PMOP.

Review

30 January 2024

Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases

Xiaxia Wang

, 9 more and

Chunlu Yan

Rheumatoid arthritis (RA) and postmenopausal osteoporosis (PMOP) are common bone-immune diseases. The imbalance between helper (Th17) and regulatory T cells (Tregs) produced during differentiation of CD4⁺ T cells plays a key regulatory role in bone remodelling disorders in RA and PMOP. However, the specific regulatory mechanism of this imbalance in bone remodelling in RA and PMOP has not been clarified. Identifying the regulatory mechanism underlying the Th17/Treg imbalance in RA and PMOP during bone remodelling represents a key factor in the research and development of new drugs for bone immune diseases. In this review, the potential roles of Th17, Treg, and Th17/Treg imbalance in regulating bone remodelling in RA and PMOP have been summarised, and the potential mechanisms by which probiotics, traditional Chinese medicine compounds, and monomers maintain bone remodelling by regulating the Th17/Treg balance are expounded. The maintenance of Th17/Treg balance could be considered as an therapeutic alternative for the treatment of RA and PMOP. This study also summarizes the advantages and disadvantages of conventional treatments and the quality of life and rehabilitation of patients with RA and PMOP. The findings presented her will provide a better understanding of the close relationship between bone immunity and bone remodelling in chronic bone diseases and new ideas for future research, prevention, and treatment of bone immune diseases.

6,156 views

7 citations

Original Research

10 January 2024

TCRβ clones in muscle tissue share structural features in patients with idiopathic inflammatory myopathy and are associated with disease activity

Dornatien C. Anang

, 10 more and

Niek de Vries

1,524 views

3 citations

(A) Upper panels: Thymus of IL21R-/- mice and littermate WT mice on embryonic day 18.5 was analyzed. Representative flow cytometric analyses of TCRγ/δ vs. CD3 on CD4-CD8- (DN) T cells, RORγt vs. IL-17A on γδT cells, and CCR9 vs. Vγ4 on γδT17 (RORγt+IL-17+) cells are shown. Lower panels: The frequencies of RORγt+IL-17+CCR9+ fetal natural γδT17 (nγδT17) cells and Vγ4+ and Vγ4- fetal nγδT17 cells among the total γδT cells and their absolute numbers are shown. n=3 for WT mice, n=5 for IL21R-/- mice. (B, C) Upper panels: Spleen (B) and lungs (C) of naïve IL21R-/- mice and littermate WT mice were analyzed at 8 weeks of age. Representative flow cytometric analyses of TCRγ/δ vs. CD3 on CD11b- live cells, RORγt vs. IL-17A on γδT cells, and Vγ4 vs. IL-17A on γδT17 cells are shown. Lower panels: The frequencies of RORγt+IL-17+nγδT17 cells, Vγ4+nγδT17 cells, and Vγ4-nγδT17 cells among the total γδT cells and their absolute numbers are shown. n=8-9, each. (D) Upper panels: Representative flow cytometric analyses of Ki-67 vs. RORγt on Vγ4+RORγt+ γδT cells and Vγ4–RORγt+ γδT cells in naïve WT and IL21R-/- mice are shown. Lower panels: The frequencies of Ki-67+ cells among Vγ4+RORγt+γδT cells and Vγ4–RORγt+ γδT cells are shown. n = 4, each. (E) Upper panels: Representative flow cytometric analyses of Annexin V vs. DAPI on Vγ4+CD27- γδT cells and Vγ4-CD27- γδT cells in naïve WT and IL21R-/- mice are shown. Lower panels: The frequencies of Annexin V+ DAPI- early apoptotic cells among Vγ4+CD27- γδT cells and Vγ4-CD27- γδT cells are shown. n = 4 each NS, not significant, *p<0.05, unpaired t-test.

Brief Research Report

18 August 2023

IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells

Junichi Ishikawa

, 9 more and

Hiroshi Nakajima

2,547 views

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(A) The proportion of innate and adaptive immune cells infiltrating the glandular tissue was analyzed by the CIBERSORT algorism based on the degree of Tfh cells infiltration. (B) The violin diagram depicted the enriching level of innate and adaptive immune cells in the Tfh-high and Tfh-low clusters evaluated by the ssGSEA algorithm. Red bold font represents the groups of immune cells with significant differences. (C, D) Correlation analysis of infiltration between different immune cell populations in the Tfh-high (C) and Tfh-low (D) clusters. (E) Correlation analysis between Tfh cells and immune cell populations. (F) The scatter plot depicted the correlation between Tfh cells and representative immune cells.

Original Research

10 August 2023

Unraveling the transcriptome-based network of tfh cells in primary sjogren syndrome: insights from a systems biology approach

Danyang Luo

, 10 more and

Liting Jiang

3,594 views

2 citations

(A) Heatmaps of mRNA-seq analysis are shown, and significant differential clustering can be found between gene expression in patients with vitiligo and normal controls (Vitiligo: N=3, HC: N=3). (B) Volcano plots of upregulated (red) and downregulated (blue) genes are shown. (C) In the enrichment analysis of signal pathways, the top enrichment pathway was the PPAR signaling pathway. (D) There is a clear clustering of the expression of LEP and LEPR between vitiligo and healthy controls. (E) The different expression of LEP and LEPR were verified by RT-qPCR (Vitiligo: N=12, HC: N=9). *P < 0.05.

Original Research

03 May 2023

Leptin deficiency in CD8+ T cells ameliorates non-segmental vitiligo by reducing interferon-γ and Granzyme B

Meiyu Wu

, 5 more and

Huiming Zhang

Background: Vitiligo is an autoimmune skin disease mainly mediated by CD8⁺ T cells, which affects about 0.1%-2% population of the world. Leptin plays a critical role in regulating the activation of CD8⁺ T cells. However, the effect of Leptin on vitiligo remains unclear.

Objectives: To explore the effect of leptin on CD8⁺ T cells and its influence on vitiligo.

Methods: RNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on Leptin KO mice.

Results: 557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that LEPR expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-γ subset of CD8⁺LEPR⁺ T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-γ was significantly increased after leptin stimulation in vitro (p = 0.0217). In mice, Leptin deficiency resulted in less severe hair depigmentation. Leptin deficiency also resulted in significantly lower expressed vitiligo-related genes, such as Cxcl9 (p = 0.0497), Gzmb (p < 0.001), Ifng (p = 0.0159), and Mx1 (p < 0.001) after modeling.

Conclusion: Leptin could promote the progression of vitiligo by enhancing the cytotoxic function of CD8⁺ T cells. Leptin may become a new target for vitiligo treatment.

4,452 views

5 citations