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

English version

Autoři: Liselotte Bäckdahl ^aff001; Mike Aoun ^aff001; Ulrika Norin ^aff001; Rikard Holmdahl ^aff001
Působiště autorů: Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden ^aff001; The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an, China ^aff002
Vyšlo v časopise: Identification of Clec4b as a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008788
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008788

Souhrn

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 controls 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⁺/MHCII^hi/CD11b/c⁺. We found that Clec4b limited the activation of arthritogenic CD4+αβT cells and the absence of Clec4b 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 both in vitro and in vivo. We conclude that Clec4b 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.

Klíčová slova:

Arthritis – Dendritic cells – Gene expression – Immune response – Intradermal injections – Oils – Spleen – T cells

Zdroje

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