MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis

Abstract

Mucosal-associated invariant T (MAIT) cells are antimicrobial T cells abundant in the gut, but mechanisms for their migration into tissues during inflammation are poorly understood. Here, we used acute pediatric appendicitis (APA), a model of acute intestinal inflammation, to examine these migration mechanisms. MAIT cells were lower in numbers in circulation of patients with APA but were enriched in the inflamed appendix with increased production of proinflammatory cytokines. Using the patient-derived appendix organoid (PDAO) model, we found that circulating MAIT cells treated with inflammatory cytokines elevated in APA up-regulated chemokine receptors, including CCR1, CCR3, and CCR4. They exhibited enhanced infiltration of Escherichia coli –pulsed PDAO in a CCR1-, CCR2-, and CCR4-dependent manner. Close interactions of MAIT cells with infected organoids led to the PDAO structural destruction and death. These findings reveal a previously unidentified mechanism of MAIT cell tissue homing, their participation in tissue damage in APA, and their intricate relationship with mucosal tissues during acute intestinal inflammation in humans.

Insights into the tissue repair features of MAIT cells

“…Additionally, these models can help describe the crosstalk between MAIT cells and resident mucosal immune cells and the consequent impacts on mucosal integrity and immunity. Recently, this technology has been applied to study MAIT cells in acute intestinal inflammation ( 125 ). In patient-derived appendiceal organoid (PDAO) models, circulating MAIT cells upregulated chemokine receptors and showed enhanced E. coli -pulsed PDAO infiltration in a CCR1-, CCR2-, and CCR4-dependent manner ( 125 ).…”

“…Recently, this technology has been applied to study MAIT cells in acute intestinal inflammation ( 125 ). In patient-derived appendiceal organoid (PDAO) models, circulating MAIT cells upregulated chemokine receptors and showed enhanced E. coli -pulsed PDAO infiltration in a CCR1-, CCR2-, and CCR4-dependent manner ( 125 ). This serves as an excellent preclinical model for investigating the roles of MAIT cells in mucosal organs.…”