Thesis: Laure Ricard – Follicular helper T cells in systemic sclerosis
September 16 - 2019
directed by Béatrice Gaugler & Arsène Mekinian
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, vascular microangiopathy and deregulated immune system with the presence of autoantibodies. Follicular helper T (Tfh) cells, defined as 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, and Tfh cells can infiltrate the skin of SSc patients. We demonstrate that cTfh cell are increased in SSc patients compared with healthy controls (HC), and this increase was more potent in severe forms of SSc. cTfh cells from SSc patients present an activated phenotype, with high expression of BCL-6 and increased capacity to produce IL-21 in comparison to HC. In vitro, cTfh cells from SSc patients had higher capacity to stimulate the differentiation of plasmablasts and their secretion of Ig through the IL-21 pathway. Blocking IL-21 or using the JAK1/2 inhibitor (ruxolitinib) reduced the Tfh cells’ capacity to stimulate the plasmablasts and decreased the Ig production. Mechanisms leading to this aberrant cTfh expansion remain to be established.