Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death.

ABSTRACT: SHARPIN, together with RNF31/HOIP and RBCK1/HOIL1, form the linear ubiquitin chain assembly complex (LUBAC) E3 ligase that catalyzes M1-linked polyubiquitination. Mutations in RNF31/HOIP and RBCK/HOIL1 in humans and Sharpin in mice lead to autoinflammation and immunodeficiency, but the mechanism underlying the immune dysregulation remains unclear. We now show that the phenotype of the Sharpin^cpdm/cpdm mice is dependent on CYLD, a deubiquitinase previously shown to mediate removal of K63-linked polyubiquitin chains. Dermatitis, disrupted splenic architecture, and loss of Peyer's patches in the Sharpin^cpdm/cpdm mice were fully reversed in Sharpin^cpdm/cpdm Cyld^-/- mice. We observed enhanced association of RI

SUBMITTER: Ang RL 

PROVIDER: S-EPMC8685717 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature