Clinical relevance of T follicular helper cells in systemic lupus erythematosus

ABSTRACT

Introduction

T helper cells regulate a variety of immune responses and are involved in the pathogenesis of infection, allergy and autoimmune diseases. T follicular helper (Tfh) cells, which induce B cell maturation, play an important role in the production of the extremely diverse autoantibodies found in systemic lupus erythematosus (SLE).

Area covered

We provide an overview of the plasticity and diversity of Tfh cells in humans and their involvement in the pathology and pathogenesis of SLE. Our review outlines the potential of Tfh cells as a therapeutic target for SLE.

Expert opinion

Tfh cells are involved in the pathogenesis of SLE based on their plasticity and diversity. Tfh cell differentiation and function are variably regulated by cytokines (IL-12, interferons, IL-2, etc), co-stimulatory molecules (ICOS, CD40L, OX40, etc), and intracellular signals (JAK-STAT, etc). Elucidation of the mechanisms underlying Tfh cell differentiation and function may lead to the development of new therapies for SLE.

KEYWORDS:

• Diversity
• plasticity
• systemic lupus erythematosus
• T follicular helper cells

Article highlights

• Tfh cells are T helper subset that induce B cell maturation and activation and antibody production.

• Activation of Tfh cells is associated with disease activity and autoantibodies production in SLE.

• Tfh cells are rich in plasticity and diversity of differentiation and function and are involved in the pathogenesis of SLE.

• Tfh cells are a promising therapeutic target for the development of molecular-targeted drugs for patients with SLE.

Declaration of interest

S Nakayamada has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, GlaxoSmithKline, Chugai, Sanofi, Pfizer, Astellas, Asahi-kasei, Boehringer Ingelheim and has received research grants from Mitsubishi-Tanabe, Novartis, and MSD. Y Tanaka has received lecture fees and/or honoraria from Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, research grants from Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo and consultation fees from Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK, Abbvie.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part by a Grant-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan (#JP20K08815, JSPS KAKENHI), and a grant from the University of Occupational and Environmental Health, Japan, through UOEH Grant for Advanced Research.