A CVID-associated variant in the ciliogenesis protein CCDC28B disrupts immune synapse assembly.

ABSTRACT: Ciliogenesis proteins orchestrate vesicular trafficking pathways that regulate immune synapse (IS) assembly in the non-ciliated T-cells. We hypothesized that ciliogenesis-related genes might be disease candidates for common variable immunodeficiency with impaired T-cell function (T-CVID). We identified a heterozygous, predicted pathogenic variant in the ciliogenesis protein CCDC28B present with increased frequency in a large CVID cohort. We show that CCDC28B participates in IS assembly by regulating polarized T-cell antigen receptor (TCR) recycling. This involves the CCDC28B-dependent, FAM21-mediated recruitment of the actin regulator WASH to retromer at early endosomes to promote actin polymerization. The CVID-associated CCDC28B^R25W variant failed to interact with FAM21, leadin

SUBMITTER: Capitani N 

PROVIDER: S-EPMC8738737 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature