1. Activation of circulating TFH17 cells associated with activated naive and double negative 2 B cell expansion, and disease activity in systemic lupus erythematosus patients.
- Author
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Khunsri T, Thawornpan P, Tianpothong P, Suangtamai T, Ngamjanyaporn P, Leepiyasakulchai C, Wangriatisak K, Pisitkun P, and Chootong P
- Subjects
- Humans, Female, Adult, Male, Middle Aged, B-Lymphocytes immunology, Lymphocyte Activation immunology, T Follicular Helper Cells immunology, Th17 Cells immunology, Young Adult, Antibodies, Antinuclear immunology, Antibodies, Antinuclear blood, Lupus Erythematosus, Systemic immunology, Lupus Erythematosus, Systemic blood
- Abstract
Background: Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4
+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear., Methods: Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed., Results: In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies., Conclusion: SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE., (© 2024. The Author(s).)- Published
- 2024
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