2025/01/14 by Aditya Josyula, Daphna Fertil, Devon R. Hartigan +8 · 1 voice
Immunology and Microbiology · Medicine · #T-cell and B-cell Immunology #Immune Cell Function and Interaction #CAR-T cell therapy research
paper · pdf · doi:10.1101/2025.01.13.632166
openalex publication_date 2025/01/14 · openalex created_date 2025/01/15 · openalex updated_date 2026/07/15
SUMMARY Self-antigens that are obscure to immune cells under homeostasis, are exposed following tissue damage and can trigger autoimmunity. Our previous work showed that conventional type 1 dendritic cells (cDC1s) mediate immunoregulation after traumatic skeletal muscle injury. Here, we found that, immune responses to injury in cDC1-depleted mice ( Batf3 -/- ) mirror those of autoimmune mice ( Aire -/- ). Mechanistically, we determined that cDC1s prime killer regulatory T cells (CD8 +/- Ly49 + Tregs) which express Ly49 inhibitory receptors and HELIOS. These killer-like Tregs are clonally diverse and carry T cell receptors associated with self-reactivity and response to hydrophobicity. cDC1 or CD8 deletion promoted CD62L + CCR7 + naïve T cell retention and B cell recruitment to injured muscle. These naïve T cells, which are implicated in autoimmunity, strongly correlate with B cell abundance in the muscle and are selectively pruned by CD8 +/- Ly49 + Tregs. Furthermore, clinically used materials that promote wound healing enrich CD8 +/- Ly49 + Treg function whereas those that are associated with pathology promote naïve T cell and B cell accumulation. We hypothesize that CD8 +/- Ly49 + Tregs maintain self-tolerance after tissue damage and avert autoimmunity by eliminating naive T cells and preventing pathogenic B cell activation.