Regulation and dysregulation of CARD14 signalling and its physiological consequences in inflammatory skin disease

• Published in: Cellular immunology Vol. 354; p. 104147
• Main Author: Mellett, Mark
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2020
• Subjects: Atopic dermatitis; BCL10; CARD14/CARMA2; Inflammation; Keratinocytes; MALT1; NF-κB; Pityriasis rubra pilaris; Psoriasis; DD; LoF; ABC-DLBCL; GWAS; TRAF; CARMA; GPP; JNK; TAB2/3; RIG-I; RNF; BIMP2; AP-1; CARD; PRP; NF-κB; PRR; Erk1; GDP; PsV; Th; CARD14/CARMA2; Atopic dermatitis; GUK; LC3; CARD14fl; AD; Ubc13; Syk; Keratinocytes; PKC; GMP; Uev1A; MAPK; p62; IκBα; LCE; BCR; ITAM; IL-17; GPCR; ULK2; Cbl-b; LPA; CARD14; NEMO; NK; Ig; GoF; FLG; DLBCL; TCR; RTK; Pityriasis rubra pilaris; BCL10; CaMK2; NOD2; CAPE; TANK; EGFR; MALT1; MKK7; AGEP; CBM; MDA5; ZAP-70; PPP; MAGUK; NEDD; TAK1; HOIL-1; BENTA; cIAP; PSORS; Psoriasis; PMA; POLKADOTS; VEGF; ERAP1; PDZ; IKK; AKT; Inflammation; LUBAC; CARD14sh; CYLD; PAMP; ITCH; MAVS; HER; ATL; CARD14cl; DC; PsA; SH3
• ISSN: 0008-8749; 1090-2163; 1090-2163
• DOI: 10.1016/j.cellimm.2020.104147

•CARD14 orchestrates the inflammatory response at the epidermal barrier.•Mutations in the CARD14 gene are associated with chronic inflammatory skin disease.•Signalling from the CARD14 complex is subject to multiple levels of regulation.•Card14 gain-of-function mutations cause spontaneous psoriasiform disease in mice. CARD14 is a scaffold molecule predominantly expressed in keratinocytes and genetic variants in the CARD14 gene confer an increased risk of inflammatory skin disease. Due to its association with common skin diseases psoriasis and atopic dermatitis, the biological function of CARD14 is of relevant interest to human health. CARD14 recruits BCL10 and MALT1 to form the CARD-BCL10-MALT1 complex, which modulates NF-κB and MAPK signalling pathways, yet little is known about how CARD14 is regulated or activated in the context of the innate immune response and in chronic inflammation. This review summarises the current understanding of the molecular function and regulatory mechanisms of CARD14 and highlights recent findings in human disease and murine mouse models.