Microplastics disrupt a cDC1-CD8/NKT regulatory circuit that restrains plasma cell accumulation after injury

Traumatic injury exposes abundant self-antigens while simultaneously mounting a significant inflammatory response to counter infection and clear debris. While canonical regulatory T cells have been implicated in recovery from sterile injury, mechanisms of peripheral tolerance maintenance in clinically relevant models with wound contamination or material implants are unknown. Here, we identify a cDC1-dependent Ly49+ CD8/NKT-like immunoregulatory pathway that restrains autoreactive responses via Fas-mediated pruning of autoreactive immune cells. Microplastic contamination shifts this balance by limiting engagement of this pathway, thereby promoting the formation of tertiary lymphoid structures, local plasma cell generation, and autoantibody production, including insulin-reactive IgG and IgA. These findings identify a mechanism of immune regulation that restrains autoreactive responses after traumatic injury that is disrupted by persistent hydrophobic microplastic contaminants.