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Nat Rev Rheumatol. 2019 Aug;15(8):475-490. doi: 10.1038/s41584-019-0254-2. Epub 2019 Jul 9.

T follicular helper cells and T follicular regulatory cells in rheumatic diseases.

Deng J1,2,3, Wei Y4, Fonseca VR5,6, Graca L7,8, Yu D9,10,11,12.

Author information

1
China-Australia Centre for Personalised Immunology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
3
Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Minda Hospital of Hubei Minzu University, Enshi, Hubei, China.
4
Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.
5
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
6
Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisboa, Portugal.
7
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. lgraca@medicina.ulisboa.pt.
8
Instituto Gulbenkian de Ciência, Oeiras, Portugal. lgraca@medicina.ulisboa.pt.
9
China-Australia Centre for Personalised Immunology, Shanghai Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. di.yu@anu.edu.au.
10
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia. di.yu@anu.edu.au.
11
Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Minda Hospital of Hubei Minzu University, Enshi, Hubei, China. di.yu@anu.edu.au.
12
Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China. di.yu@anu.edu.au.

Abstract

As a hallmark of autoimmune rheumatic diseases, autoantibodies have been used in diagnosis for decades. However, the immunological mechanism underlying their generation has only become clear following the identification of T follicular helper (TFH) cells and T follicular regulatory (TFR) cells. TFH cells are instrumental in supporting antibody affinity maturation in germinal centre reactions and humoral memory formation, whereas TFR cells suppress TFH cell-mediated antibody responses. Evidence indicates that patients with autoimmune rheumatic diseases have increased numbers of TFH cells that can be hyperactive, and also potentially have altered numbers of TFR cells with reduced function, suggesting a conceivable dysregulation in the balance between TFH cells and TFR cells in these diseases. Therefore, by identifying the molecular mechanisms underlying the development and function of these cell populations, new opportunities have emerged to develop novel therapeutic targets. An increased knowledge of TFH cells and TFR cells has inspired, and hopefully will inspire more, approaches to reinstate the balance of these cells in the prevention and treatment of rheumatic diseases.

PMID:
31289377
DOI:
10.1038/s41584-019-0254-2

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