Intestinal Permeability and IgA Provoke Immune Vasculitis Linked to Cardiovascular Inflammation.

ABSTRACT: Recent experimental data and clinical, genetic, and transcriptome evidence from patients converge to suggest a key role of interleukin-1? (IL-1?) in the pathogenesis of Kawasaki disease (KD). However, the molecular mechanisms involved in the development of cardiovascular lesions during KD vasculitis are still unknown. Here, we investigated intestinal barrier function in KD vasculitis and observed evidence of intestinal permeability and elevated circulating secretory immunoglobulin A (sIgA) in KD patients, as well as elevated sIgA and IgA deposition in vascular tissues in a mouse model of KD vasculitis. Targeting intestinal permeability corrected gut permeability, prevented IgA deposition and ameliorated cardiovascular pathology in the mouse model. Using genetic and pharmacologic inhibition of IL-1? signaling, we demonstrate that IL-1? lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Targeting mucosal barrier dysfunction and the IL-1? pathway may also be applicable to other IgA-related diseases, including IgA vasculitis and IgA nephropathy.

SUBMITTER: Noval Rivas M 

PROVIDER: S-EPMC6751009 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature