invariant natural killer t cells regulate conventional dendritic cell maturation to re-establish immune tolerance to rheumatoid arthritis in dba/1 mice

Rheumatoid arthritis (ra) is a type of autoimmune disease that results in immune disorder and excessive inflammatory response due to a reduction of self-tolerance. invariant natural killer t (inkt) cells can effectively alleviate clinical symptoms and hyper-inflammation in ra, but their mechanism of action is not well-defined. this study aims to investigate the mechanism of inkt cell therapy for ra.we established a dba/1 mouse model for ra and treated it with specific inkt cells. a cytometric bead array was used to measure the amounts of cytokines in the serum. flow cytometry was then employed to identify different subsets of helper t cells (th), the frequency of conventional dendritic cells (cdc), the expression of cd80, cd86, programmed cell death ligand 1 (pd-l1), and pd-l2 on cdc surfaces, and associated pathway proteins.inkt cell treatment reduced th1/th2 and th17/ regulatory t (treg) cell ratios while increasing interleukin-4 (il-4) and il-10. it enhanced the generation of immature cdcs, and it upregulated the level of pd-l2 by stimulating the signal transducer and activator of transcription 3 (stat3) signaling pathway. meanwhile, it activated the extracellular signal-regulated kinase 1/2 (erk1/2) pathway and inhibited the nuclear factor kappa b (nf-κb) pathway.according to our findings, inkt cell treatment increased the expression of phosphates stat3  in lymph node cdc, causing them to upregulate pd-l2 molecules. while activating the erk1/2 pathway and inhibiting the nf-κb pathway, tolerogenic cdc was produced, restoring immune homeostasis and correcting excessive inflammation. these results deliver new insights into the treatment of ra by inkt cells.