Abe Saori, Tsuboi Hiroto, Aoki Hiroyasu, Toko Hirofumi, Honda Fumika, Miki Haruka, Asashima Hiromitsu, Kondo Yuya, Matsumoto Isao
Department of Rheumatology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Sci Rep. 2025 Jul 2;15(1):23520. doi: 10.1038/s41598-025-07008-3.
Understanding the intricate relationship between peripheral blood immune profiles and the inflammatory environment within affected tissues is pivotal for uncovering mechanisms driving autoimmune diseases. This study aimed to characterize CD4 T cell subsets in peripheral blood that mirror the immunological activation of labial salivary glands (LSG) infiltrating T cells in primary Sjögren's disease (pSjD). Using multicolor flow cytometry and T cell receptor (TCR) sequencing, we identified CXCR3CXCR5 T follicular helper 1 (Tfh1) cells as significantly elevated in the circulation of pSjD patients and even more prominently increased in the LSG, with blood PD-1ICOS Tfh1 cells positively correlating with titers of antinuclear, anti-SS-A, and anti-SS-B antibodies. In contrast, CXCR3CXCR5 Th1 cells were enriched in LSG but reduced in circulation. TCR analysis demonstrated that circulating Tfh1 cells shared a notable clonal similarity with LSG T cells. In the LSG, cytokines such as IL-6, IL-12, IL-21, and TGF-β were upregulated, with TGF-β and TCR recognition promoting Tfh1 differentiation. This microenvironment led to increased production of IL-2, TNF-α, and IL-21, promoting the expansion of CD19CD38 B cells. These findings support the notion that circulating activated Tfh1 cells partially mirror glandular T cell activation and highlight TGF-β as a driver of Tfh1 differentiation, presenting a potential therapeutic target.
了解外周血免疫谱与受影响组织内炎症环境之间的复杂关系对于揭示自身免疫性疾病的发病机制至关重要。本研究旨在表征外周血中反映原发性干燥综合征（pSjD）唇腺（LSG）浸润T细胞免疫激活的CD4 T细胞亚群。通过多色流式细胞术和T细胞受体（TCR）测序，我们发现CXCR3CXCR5 T滤泡辅助细胞1（Tfh1）细胞在pSjD患者循环中显著升高，在LSG中升高更为明显，血液中PD-1ICOS Tfh1细胞与抗核抗体、抗SS-A抗体和抗SS-B抗体滴度呈正相关。相比之下，CXCR3CXCR5 Th1细胞在LSG中富集但在循环中减少。TCR分析表明，循环中的Tfh1细胞与LSG T细胞具有显著的克隆相似性。在LSG中，白细胞介素-6、白细胞介素-12、白细胞介素-21和转化生长因子-β等细胞因子上调，转化生长因子-β和TCR识别促进Tfh1分化。这种微环境导致白细胞介素-2、肿瘤坏死因子-α和白细胞介素-21产生增加，促进CD19CD38 B细胞的扩增。这些发现支持循环活化Tfh1细胞部分反映腺体T细胞活化的观点，并突出转化生长因子-β作为Tfh1分化的驱动因素，提出了一个潜在的治疗靶点。
