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

ABSTRACT: 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+/MHCIIhi/CD11b/c+. We found that Clec4b limited the activation of arthritogenic CD4+??T 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.

SUBMITTER: Backdahl L

PROVIDER: S-EPMC7297379 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Bäckdahl Liselotte L Aoun Mike M Norin Ulrika U Holmdahl Rikard R

PLoS genetics 20200604 6

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 ...[more]

PMID: 32497089

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Dataset Information

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

Publications

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

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