In vitro co-culture of RA FLSs and peripheral blood mononuclear cells (PBMCs) revealed that increased production of TNF-α, IL-1β, IL-6, and reactive oxygen species (ROS) could promote CD4 + CXCR5 + ICOS + Tfh differentiation (110). The gene discussed is CXCR5; the disease is rheumatoid arthritis.