The soluble form of CD83 (sCD83) has immunomodulatory properties, including the ability to induce tolerogenic dendritic cell and regulatory T (Treg) cell responses, but its involvement in inflammatory arthritis has, until now, been unclear. “We show for the first time that sCD83 has anti-inflammatory properties in arthritis and induces resolution of inflammation,” explains Elisabeth Zinser, co-corresponding author of a new study.

Credit: Springer Nature Limited

Given that dendritic cell activation and persistent stimulation of T cells are important contributors to the pathogenesis of rheumatoid arthritis, the researchers sought to investigate the modulatory function of sCD83 in two mouse models of arthritis: antigen-induced arthritis (AIA) and K/B×N serum transfer-induced arthritis.

“Interestingly, sCD83 treatment not only reduced joint swellings, but also inhibited expression of important pro-inflammatory cytokines,” reports co-corresponding author Alexander Steinkasserer.

In the AIA model, administration of sCD83 accelerated the resolution of inflammation compared with administration of saline. sCD83 also inhibited the expression of receptor activator of nuclear factor-κB ligand (RANKL), a regulator of osteoclast differentiation, potentially explaining the sCD83-mediated reduction in osteoclast formation and attenuation of bone and cartilage destruction.

The proresolving effect of sCD83 was completely abrogated with an indoleamine 2,3-dioxygenase (IDO) inhibitor and partially abrogated with an anti-transforming growth factor-β (TGFβ) antibody.

IDO is an important modulator of T cell responses, functioning as an enzyme to convert tryptophan (an essential amino acid for T cell proliferation) into kynurenine (an inducer of Treg cell responses), and as a signalling protein to induce TGFβ expression (an important cytokine for Treg cell activity). Notably, treatment with the IDO inhibitor prevented the sCD83-induced accumulation of Treg cells.

…administration of [soluble CD83] accelerated the resolution of inflammation

The researchers hypothesize that sCD83 functions through IDO to promote the expansion of Treg cells, which induces the resolution of inflammation and inhibits osteoclast formation. “The next steps will be to further elucidate the underlying pro-resolving mechanisms induced by the sCD83-IDO axis,” explains Steinkasserer.