Cytotoxic Tph-like cells are involved in persistent tissue damage in IgG4-related disease. Issue 1 (2nd January 2021)

• Record Type: Journal Article
• Authors: Yabe, Hayato; Kamekura, Ryuta; Yamamoto, Motohisa; Murayama, Kosuke; Kamiya, Shiori; Ikegami, Ippei; Shigehara, Katsunori; Takaki, Hiromi; Chiba, Hirofumi; Takahashi, Hiroki; Takano, Kenichi; Takahashi, Hiroki; Ichimiya, Shingo
• Is Part Of: Modern rheumatology. Volume 31:Issue 1(2021)
• Page Start: 249
• Page End: 260
• Publication Date: 2021-01-02
• Subjects: CX3CR1 -- cytotoxic molecules -- fractalkine -- IgG4-related disease -- Tph-like cells; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1080/14397595.2020.1719576
• Languages: English
• ISSNs: 1439-7595

Abstract

Abstract: Objectives: The aim of this study was to determine pathological features of T peripheral helper (Tph)-like (PD-1 + CXCR5 − CD4 + T) cells in IgG4-related disease (IgG4-RD). Methods: Tph-like cells in the blood and submandibular glands (SMGs) from IgG4-RD patients were analyzed by flow cytometry. Correlations between level of a Tph-like cell subset and clinical parameters of IgG4-RD were investigated. The cytotoxic capacity of Tph-like cells was also examined. Expression profiles of a molecule related to a Tph-like cell subset in IgG4-RD SMGs were assessed by immunohistochemistry. Results: Tph-like cells from IgG4-RD patients highly expressed a fractalkine receptor, CX3CR1. Percentages of circulating CX3CR1 + Tph-like cells were significantly correlated with clinical parameters including IgG4-RD Responder Index, number of involved organs, and serum level of soluble IL-2 receptor. CX3CR1 + Tph-like cells abundantly possessed cytotoxic T lymphocyte-related molecules such as granzyme A, perforin, and G protein-coupled receptor 56. Functional assays revealed their cytotoxic potential against vascular endothelial cells and ductal epithelial cells. Immunohistochemistry showed that fractalkine was markedly expressed in vascular endothelial cells and ductal epithelial cells in IgG4-RD SMGs. Conclusion: CX3CR1 + Tph-like cells are thought to contribute to persistent tissue injury in IgG4-RD and are a potential clinical marker and/or therapeutic target for inhibiting progression of IgG4-RD.