Identification of < i > Clec4b < /i > as  a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease

by Liselotte B äckdahl, Mike Aoun, Ulrika Norin, Rikard Holmdahl The control of chronic inflammation is dependent on the possibility of limiting bystander activation of autoreactive and potentially pathogenic T cells. We have identified a non-sense loss of function single nucleotide polymorphism in the C-type lectin receptor, Clec4b, and have shown that it cont rols chronic autoimmune arthritis in rat models of rheumatoid arthritis.Clec4b is specifically expressed in CD4+ myeloid cells, mainly classical dendritic cells (DCs), and is defined by the markers CD4+/MHCIIhi/CD11b/c+. We found thatClec4b limited the activation of arthritogenic CD4+ αβT cells and the absence ofClec4b allowed development of arthritis already 5 days after adjuvant injection.Clec4b sufficient CD4+ myeloid dendritic cells successfully limited the arthritogenic T cell expansion immediately after activation bothin vitro andin vivo. We conclude thatClec4b expressed on CD4+ myeloid dendritic cells regulate the expansion of auto-reactive and potentially pathogenic T cells during an immune response, demonstrating an early checkpoint control mechanism to avoid autoimmunity leading to chronic inflammation.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research