Objectives Systemic sclerosis (SSc) is an autoimmune disease characterised by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4+CXCR5+PD-1+ cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases. However, there are no data about cTfh cells and their interaction with B cells in SSc. The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc.
Methods Using flow cytometry, we analysed cTfh cells from 50 patients with SSc and 32 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells were performed for functional analysis. IgG and IgM production were measured by ELISA.
Results We observed that cTfh cell numbers are increased in patients with SSc compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from patients with SSc present an activated Tfh phenotype, with high expression of BCL-6, increased capacity to produce IL-21 in comparison with healthy controls. In vitro, cTfh cells from patients with SSc had higher capacity to stimulate the differentiation of CD19+CD27+CD38hi B cells and their secretion of IgG and IgM through the IL-21 pathway than Tfh cells from healthy controls. Blocking IL-21R or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells’ capacity to stimulate the plasmablasts and decreased the Ig production.
Conclusions Circulating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc.
- systemic sclerosis
- T follicular helper cell
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BéaG and AènM contributed equally.
Handling editor Josef S Smolen
Contributors All authors listed on the manuscript have substantially contributed to this work. BG, LR and AM designed the experimental research, performed experiments, interpreted data and wrote the manuscript. FM, MM, VJ, SR, NS, YY, PS, J-BM and OF interpreted the data and participated in the writing of the manuscript.
Funding This work was supported by the Aterhit Foundation and received grants from ‘Groupe Francophone de Recherche sur la Sclérodermie’ (GFRS).
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval This study was approved by the Ethic committee of ‘Kremlin Bicêtre University’ (no. ID-RCB 2017-AO3380-53).
Provenance and peer review Not commissioned; externally peer reviewed.