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Novel function of hydroxychloroquine: Down regulation of T follicular helper cells in collagen-induced arthritis - 31/12/17

Doi : 10.1016/j.biopha.2017.10.132 
Jiaochan Han a, b, 1, Qingyou Zhou c, 1, Xing Li a, b, Juan He a, b, Yanping Han d, Hongyu Jie a, b, Yi He a, b, , Erwei Sun a, b,
a Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China 
b Institute of Clinical Immunology, Academy of Orthopedics, Guangdong Province, Guangzhou, China 
c Department of Neurology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, China 
d Hospital of South China Normal University, Guangzhou, China 

Corresponding authors at: Department of Rheumatology and Immunology, The Third Affiliated Hospital of Southern Medical University, No. 183, Zhongshan Avenue West, Tianhe District, Guangzhou 510630, China.Department of Rheumatology and ImmunologyThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina

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Highlights

The proportion of circulating Tfh cells is increased in RA patients.
HCQ reduces the proportion of Tfh cells in PBMCs and purified CD4+ T cells in healthy volunteers.
HCQ prevents the development of CIA by down-regulating the proportion of Tfh cells.
The effect of HCQ on Tfh cells relates to IL-12 and IL-21 signaling pathways.

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Abstract

Hydroxychloroquine (HCQ) is an immunosuppressive agent widely used in rheumatoid arthritis (RA). T follicular helper (Tfh) cells play a vital role in the pathogenesis of RA. However, whether HCQ suppresses arthritis development through interfering with Tfh cells have never been reported. To address this issue, we investigated the percent of Tfh cells in newly diagnosed RA patients and found that they were up-regulated in peripheral blood. Importantly, in ex vivo experiments of peripheral blood mononuclear cells (PBMCs) from healthy volunteers, we proved that the percentage of Tfh cells in PBMCs and purified CD4+ T cells were decreased after HCQ treatment. In in vivo experiments of collagen-induced arthritis (CIA) model, we discovered that HCQ suppressed the incidence and score of arthritis, reduced the secretion of proinflammatory cytokines in serum. Similar to ex vivo study, the ratio of Tfh cells in HCQ treated CIA mice declined to the level of vehicle-treated group. Further research demonstrated that HCQ inhibited the generation of Tfh cells stimulated by IL-12 and IL-21. In conclusion, our study indicates a previously unrecognized mechanism of HCQ in RA, that HCQ directly suppresses the generation of Tfh cells by blocking IL-12 and IL-21 signaling pathways probably.

El texto completo de este artículo está disponible en PDF.

Keywords : Rheumatoid arthritis, T follicular helper cells, Hydroxychloroquine


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© 2017  Elsevier Masson SAS. Reservados todos los derechos.
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Vol 97

P. 838-843 - janvier 2018 Regresar al número
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