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T follicular helper cells and T peripheral helper cells in rheumatic and musculoskeletal diseases
  1. Mitsuhiro Akiyama,
  2. Waleed Alshehri,
  3. Keiko Yoshimoto,
  4. Yuko Kaneko
  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Japan
  1. Correspondence to Dr Mitsuhiro Akiyama, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, 160-8582, Japan; mitsuaki{at}keio.jp; Dr Yuko Kaneko; ykaneko.z6{at}keio.jp

Abstract

Recent technological progress has greatly advanced our understanding of human immunology. In particular, the discovery of human T follicular helper (Tfh) and T peripheral helper (Tph) cells has significantly advanced our understanding of human adaptive immune system. Tfh and Tph cells share similar molecular characteristics and both play critical roles in B cell differentiation and maturation. However, they differ in their functional properties, such as chemokine receptor expression and cytokine production. As a result, Tfh cells are mainly involved in B cell differentiation and maturation in germinal centres of secondary lymphoid tissues, while Tph cells are involved in B cell differentiation and tissue damage in peripheral inflammatory lesions. Importantly, the involvement of Tfh and Tph cells in the pathogenesis of rheumatic and musculoskeletal diseases has become clear. In rheumatoid arthritis and systemic lupus erythematosus, Tph cell infiltration is predominant in peripheral inflammatory lesions, whereas Tfh cell infiltration is predominant in the affected lesions of IgG4-related disease. Therefore, the contribution of Tfh and Tph cells to the development of rheumatic and musculoskeletal diseases varies depending on each disease. In this review, we provide an overview of human Tfh and Tph cells and summarise the latest findings on these novel T cell subsets in various rheumatic and musculoskeletal diseases.

  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus
  • Immune System Diseases
  • T-Lymphocyte subsets
  • Autoimmune Diseases

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors Study design: MA and YK. Data acquisition: MA and KY. Data analysis and interpretation: MA. Manuscript drafting: MA and WA. All authors approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MA has received speaker fees from Asahikasei, Astellas, Boehringer Ingelheim, Eli Lilly, Pfizer and UCB. YK has received grants or speaker fees from AbbVie, Asahikasei, Astellas, Ayumi, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi and UCB. WA and KY declare no conflicts of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.