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Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals

ABSTRACT: Microbiota composition regulates colitis severity, yet mechanisms employed by the innate immune system to regulate this remain unclear. We show that severity of colitis in Clec12a deficient animals is dependent on microbiota composition. Microbiota from a Clec12a-/- animal has expanded Faecalibaculum rodentium and transplantation of the Clec12a-/- microbiota or treatment with F. rodentium is sufficient to worsen colitis in wild-type mice. However, Clec12a-/- animals are resistant to colitis developmemt when rederived into an 11-member community, while addition of F. rodentium worsens disease. Colitis in Clec12a-/- mice is dependent on monocytes and cytokine and sequencing analysis in Clec12a-/- macrophages and serum shows enhanced inflammation with a reduction in phagocytic genes. We demonstrate that F. rodentium specifically binds to Clec12a and Clec12a-/- deficient macrophages are specifically impaired in their ability to phagocytose F. rodentium. Thus, Clec12a is an innate-immune surveillance mechanism to control the expansion of potentially harmful commensals while limiting inflammation

ORGANISM(S): Mus musculus

PROVIDER: GSE283366 | GEO | 2025/02/19

REPOSITORIES: GEO

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