mechanism of pd-1/pd-l1 in regulating ctfr/ctfh balance in patients with rheumatoid arthritis

Rheumatoid arthritis (ra) is frequent, an imbalance between helper cells (th) and regulatory t cells (treg) is the fundamental immunological cause of ra. this study investigates how recombinant human programmed cell death 1 (pd-l1) protein affects circulating t follicular helper (ctfh), circulating t follicular regulatory (ctfr), and their equilibrium.magnetic bead sorting was used to select cd4+cxcr5+t cells from ra patients' and healthy individuals' peripheral blood mononuclear cells for in vitro growth. recombinant human pd-l1 protein stimulated cd4+cxcr5+t cells. cell counting kit 8 (cck-8), flow cytometry surface labeling, elisa, and rt-pcr were used to measure cd4+cxcr5+t cell proliferation inhibition, ctfh and ctfr frequencies, il-21 expression, and pi3k, akt, bcl-6, and blimp-1 mrna levels. the recombinant human pd-l1 protein dose-dependently inhibited the proliferation of cd4+cxcr5+t cells in active ra peripheral blood. however, it has a weaker inhibitory effect on healthy peripheral blood cd4+cxcr5+t cells. pd-l1 protein decreased ctfh in active ra peripheral blood cd4+cxcr5+t overall cultured cells but did not affect ctfr; the ctfr/ctfh ratio increased but did not affect the frequency of ctfh and ctfr in healthy persons' cultured cd4+cxcr5+t cells. pd-l1 protein reduced il-21 in cd4+cxcr5+t cell culture supernatant from active ra peripheral blood. recombinant human pd-l1 protein lowered pi3k, akt, and bcl-6 mrna in active ra peripheral blood cd4+cxcr5+t cell culture, including significant differences. but blinmp-1 mrna variations were neither substantial nor statistically different.pd-1/pd-l1 limits ctfh proliferation, differentiation, and activation via the pi3k/akt signaling pathway regulates its immunological balance with ctfr, and corrects the ctfr/ctfh imbalance by controlling their interaction.