A human immunodeficiency syndrome caused by mutations in CARMIL2

作者：Schober T; Magg T; Laschinger M; Rohlfs M; Linhares N D; Puchalka J; Weisser T; Fehlner K; Mautner J; Walz C; Hussein K; Jaeger G; Kammer B; Schmid I; Bahia M; Pena S D; Behrends U; Belohradsky B H; Klein C^*; Hauck F

来源：Nature Communications, 2017, 8(1): 14209.

DOI：10.1038/ncomms14209

Human T-cell function is dependent on T-cell antigen receptor (TCR) and co-signalling as evidenced by immunodeficiencies affecting TCR-dependent signalling pathways. Here, we show four human patients with EBV+ disseminated smooth muscle tumours that carry two homozygous loss-of-function mutations in the CARMIL2 (RLTPR) gene encoding the capping protein regulator and myosin 1 linker 2. These patients lack regulatory T cells without evidence of organ-specific autoimmunity, and have defective CD28 co-signalling associated with impaired T-cell activation, differentiation and function, as well as perturbed cytoskeletal organization associated with T-cell polarity and migration disorders. Human CARMIL2-deficiency is therefore an autosomal recessive primary immunodeficiency disorder associated with defective CD28-mediated TCR co-signalling and impaired cytoskeletal dynamics.

• 出版日期2017-1-23