Putting JNK1 on the immunodeficiency map

Abstract

Immunodeficiencies Impaired T helper 17 cell immunity is the shared element among a group of inherited immunodeficiencies that are associated with chronic mucocutaneous candidiasis (CMC). Li et al. studied three patients from a single family who had a combination of CMC and an atypical form of connective tissue disorder that had some features of Ehlers-Danlos syndrome. Whole-exome sequencing identified a loss-of-function splice-site mutation in the MAPK8 gene encoding c-Jun N-terminal kinase 1 (JNK1) that causes JNK1 haploinsufficiency with autosomal dominant inheritance. The complex clinic al phenotype in these patients results from defects in signaling downstream of both interleukin-17 and transforming growth factor–β (TGF-β) cytokines. Thus, JNK1-mediated signaling plays a critical role in maintaining normal immunity to Candida , and TGF-β promotes homeostasis of connective tissues. Sci. Immunol. 4 , eaax7965 (2019).