CCR2 and CCR5 Expression on Tph Cells Is Associated with IL-21 and Renal Involvement in Systemic Lupus Erythematosus

Background/Objectives: The increased frequency of circulating T follicular helper (cTfh) and T peripheral helper (Tph) cells in patients with systemic lupus erythematosus (SLE) and their association with higher disease activity have been reported. However, their role in the immunopathogenesis of SLE remains unclear. CCR2 and CCR5 have been identified on the surface of cTfh and Tph cells in autoimmune diseases such as Sjögren’s Disease. Methods: This study evaluates the association between CCR2+CCR5+cTfh and CCR2+CCR5+Tph cell frequencies and serum cytokine levels in patients with SLE and lupus nephritis (LN). Results: SLE patients showed higher frequencies of cTfh and Tph cells. Overall, CCR2 and CCR5 expression was higher in Tph cells than in cTfh cells. The frequency of CCR5+Tph and CCR5+cTfh cells was higher in patients with proliferative LN than in those with mixed-type LN. IL-21 correlated with the frequency of CCR2+CCR5+ Tph cells. In renal tissue, expression of CD4, CXCR5, CCR5, and CCR2 was more prominent in tubulo-interstitial areas with predominantly chronic lesions. Conclusions: Our results provide information on the expression of CCR2 and CCR5 in cTfh and Tph cells in SLE and offer insights into the association with inducing cytokines, highlighting the potential role of these cells in LN.