Imbalance toward T<subscript>FH</subscript> 1 cells playing a role in aberrant B cell differentiation in systemic sclerosis.

Objective SSc is a connective tissue disease with multisystem disorder induced by the inflammation and fibrosis following T and B cell abnormalities. Follicular helper CD4 + T (T FH ) cells play a crucial role in the formation of germinal centres and specialize in interacting to aid B cell differentiation. We aimed to investigate T FH cells and their subsets to evaluate their involvement with B cell alteration in SSc. Method Circulating T FH cells (cT FH ), B cells and their subsets were assessed by flow cytometry. The concentration of serum cytokines was measured by cytokine array assay. Immunohistochemistry and IF were performed to evaluate the migration of T FH cells in SSc skin lesions. Results The proportion of cT FH cells did not differ from controls, but their subsets were imbalanced in SSc patients. The frequency of T FH 1 was increased and correlated with ACA titre, serum IgM or CRP levels of patients, and cytokine concentrations of IL-21 and IL-6 that induce B cell differentiation in SSc. cT FH cells from SSc showed activated phenotype with expressing higher cytokine levels compared with controls. The frequency of T FH 17 was also increased, but was not correlated with a high level of Th17 cytokines in patients' sera. Furthermore, infiltration of T FH cells was found in skin lesion of SSc patients. Conclusion We here describe an imbalance of cT FH toward T FH 1 that may induce B cell alteration through IL-21 and IL-6 pathways and promote inflammation, contributing to the pathogenesis of SSc disease. [ABSTRACT FROM AUTHOR]

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