Th17/IL-17A axis is critical for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc): SSc patients with high levels of serum IL-17A exhibit reduced lung functions and increased prevalence of PAH.

Autor: Seki N; Research Unit Immunology & Inflammation, Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Tsujimoto H; Research Unit Immunology & Inflammation, Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Tanemura S; Research Unit Immunology & Inflammation, Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Ishigaki S; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Takei H; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Sugahara K; Research Unit Immunology & Inflammation, Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Yoshimoto K; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Akiyama M; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Kaneko Y; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan., Chiba K; Research Unit Immunology & Inflammation, Innovative Research division, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa 227-0033, Japan; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: Chiba.Kenji@mk.mt-pharma.co.jp., Takeuchi T; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; Saitama Medical University, Iruma-gun, Saitama 350-0495, Japan.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2024 Apr; Vol. 176, pp. 156534. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1016/j.cyto.2024.156534
Abstrakt: Background: It is thought that systemic sclerosis (SSc) might be a T helper 17 (Th17) cell-driven autoimmune disease. Noticeably, pulmonary arterial hypertension (PAH) is a leading cause of death in patients with SSc. Here, we investigated the association between serum Th17-related cytokines and prevalence of PAH in SSc patients.
Methods: This study included 72 SSc patients and 51 healthy controls (HC). We determined clinical manifestations, immunophenotypes including Th subsets in peripheral blood lymphocytes, and the serum levels of interleukin (IL)-17A, IL-17A/F, IL-17B. IL-17C, IL-17D. IL-1β, IL-6, IL-21, IL-22, and IL-23.
Results: The frequency of Th17 cells was significantly increased in SSc patients compared to HC and was positively correlated with the modified Rodnan skin scores. Furthermore, the serum levels of IL-17A, IL-17D, IL-1β, and IL-6 were significantly increased in SSc patients compared to HC. SSc patients with detected IL-17A showed high levels of IL-17A/F, IL-1β, IL-6, and IL-22, and high frequency of Th17 cells. Interestingly, these patients exhibited the reduced lung functions and increased prevalence of PAH significantly compared to patients with undetected IL-17A. Similarly, SSc patients with detected IL-17A and high IL-6 (≥1.2 pg/mL) exhibited the decreased lung functions and increased prevalence of PAH compared to patients with undetected IL-17A and low IL-6.
Conclusion: We found that SSc patients with high levels of serum IL-17A or both IL-17A and IL-6 show reduced lung functions and high prevalence of PAH. Consequently, it is highly probable that Th17/IL-17A axis is critical for the prevalence of PAH in SSc patients.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mitsuhiro Akiyama: Asahikasei Pharma Corp., Astellas Pharma Inc., Boehringer Ingelheim Co., Ltd., Eli Lilly Japan KK., Pfizer Japan Inc., and UCB Japan Co., Ltd. Yuko Kaneko: AbbVie GK, Asahikasei Pharma Corp., and Eli Lilly Japan KK. Tsutomu Takeuchi: AbbVie GK, Bristol-Myers KK, Chugai Pharmaceutical Co., Ltd. Noriyasu Seki, Hideto Tsujimoto, Shuhei Tanemura, Kunio Sugahara, and Kenji Chiba: Mitsubishi Tanabe Pharma Corporation (employee).
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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