T helper cells expressing fractalkine receptor and bearing T follicular helper 1-like cell functions in patients with IgG4-related disease. (23rd December 2021)

• Record Type: Journal Article
• Authors: Inoue, Yoshino; Nakayamada, Shingo; Kubo, Satoshi; Yamagata, Kaoru; Sonomoto, Koshiro; Iwata, Shigeru; Miyazaki, Yusuke; Tanaka, Yoshiya
• Is Part Of: Rheumatology. Volume 61:Number 9(2022)
• Page Start: 3854
• Page End: 3863
• Publication Date: 2021-12-23
• Subjects: other idiopathic inflammatory disorders -- cell receptor-ligand interaction -- signalling and activation -- T cells -- lymphocytes -- cytokines and inflammatory mediators; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keab935
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objective: Because the pathological features of IgG4-related disease (IgG4-RD) include lymphocyte infiltration and fibrotic changes in the lesions, we investigated the significance of fractalkine (CX3 CL1) and lymphocyte subsets in patients with IgG4-RD. Methods: Peripheral blood and biopsied samples were obtained from healthy controls (HCs, n = 10), RA ( n = 10) and IgG4-RD patients ( n = 16) and were analysed by flow cytometry, immunohistology and costimulation assays. Results: Peripheral CX3 CR1 + CD4 + T cells had an approximately 3-fold increase in the IgG4-RD patients (15.4%), compared with the HCs (5.0%). In addition, CX3 CR1 + CD4 + T cells were localized in the salivary glands of the IgG4-RD patients but not in those with Sicca syndrome. CX3 CR1 was induced on 20% of CD4 + T cells after T-cell receptor (TCR) simulation with IL-12 for five days culture. CX3 CR1 + T cells showed high expression of both CXCR5 and CXCR3. Moreover, they co-expressed Bcl-6 and T-bet, the master transcription factors for T helper 1 (Th1) and T follicular helper (Tfh) cells. After secondary stimulation, CX3 CR1 + T cells produced both IFN-gamma (IFN-γ) and IL-21. Compared with their CX3 CR1 − counterparts, CX3 CR1 + CD4+ T cells induced plasmablast differentiation from naïve B cells more efficiently (15.0 vs 5.0%) and increased the production of IgG2, IgG3 and IgG4 by B cells. Conclusion: CX3 CR1 + CD4 + T cells characteristically increased in the peripheral blood and the affected tissues and were associated with an increase in the serum IgG4 levels of patients with IgG4-RD. This CD4 subset has a Th1/Tfh-like phenotype and a B cell helper function.