MAIT cells present in the peripheral blood and tissues in the gut and the liver ( 9, 10) actively produce interferon-γ (IFN-γ), interleukin (IL)-17, Granzyme B, and perforin in response to viral and bacterial challenges and show pro-inflammatory and cytotoxic phenotypes ( 11). Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells expressed as evolutionarily conserved invariant T-cell antigen receptors (TCRs), including semi-invariant α-chain Vα7.2-Jα33-20-12 in human and Vα19-Jα33 in mice ( 8). Thus, investigation of the pathogenesis of PBC and potential therapeutic targets is urgently needed. Fibrates, methotrexate, colchicine, azathioprine, and liver transplant are unapproved alternatives ( 6, 7). The therapeutic approaches for PBC remain limited: ursodeoxycholic acid (UDCA) and obeticholic acid (Ocaliva) are the only FDA-approved agents, with ~60% biochemical response to UDCA ( 1, 5). PBC also presents systemic involvements beyond cholangitis, including interstitial lung disease, ( 2) pulmonary hypertension ( 3), and cardiomyopathy ( 4). Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by non-suppurative inflammation and immune-mediated destruction of small intrahepatic bile ducts, portal tract fibrosis, cirrhosis, and circulating anti-mitochondrial antibodies ( 1). Targeting MAIT cells might be a therapeutic approach for PBC. 43.5 ± 4.2%, p < 0.01).Ĭonclusion: Mucosal-associated invariant T cells from patients with PBC accumulated in the liver via CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. IL-18 promoted IFN-γ production in MAIT cells (74.9 ± 6.6% vs. Plasma IL-18 was more abundant in patients with PBC (286.8 ± 75.7 pg/ml vs. MAIT cells from PBC expressed higher levels of IL18-Rα (83.8 ± 10.2% vs. MAIT cells from PBC produced significantly more interferon-γ (IFN-γ) (88.3 ± 4.2% vs. 52.2 ± 3.5%, p < 0.01), which was attenuated by CXCR4 antagonist. CXCL12 promoted MAIT cell chemotaxis (70.4 ± 6.8% vs. 58.7 ± 11.4%, p < 0.01), and the expression of CXCL12 was higher in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 ± 18.0% vs. Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. 9.4 ± 8.0%, p < 0.01) and negatively correlated with alkaline phosphatase (ALP) levels ( r = −0.3209, p < 0.05). Result: Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 ± 3.2% vs. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. ![]() Liver-resident MAIT cells were examined by immunofluorescence staining. ![]() ![]() Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Methods: We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Objectives: To explore the potential role of CD3 +CD8 +CD161 high TCRVα7.2 + mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC). 2Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.Zhilei Chen 1,2, Suying Liu 1,2, Chengmei He 1,2, Jinlei Sun 1,2, Li Wang 1,2, Hua Chen 1,2 * and Fengchun Zhang 1,2 *
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