MR1 deficiency enhances IL-17-mediated allergic contact dermatitis

Abstract

Major histocompatibility complex (MHC) class Ib molecules present antigens to subsets of T cells primarily involved in host defense against pathogenic microbes and influence the development of immune-mediated diseases. The MHC class Ib molecule MHC-related protein 1 (MR1) functions as a platform to select MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells in the thymus, and presents ligands to them in the periphery. MAIT cells constitute an innate-like T-cell subset that recognizes microbial vitamin B2 metabolites and plays a defensive role against microbes. In this study, we investigated the function of MR1 in allergic contact dermatitis (ACD) by examining wild-type (WT) and MR1-deficient (MR1-/-) mice in which ACD was induced with 2,4-dinitrofluorobenzene (DNFB). MR1-/- mice exhibited exaggerated ACD lesions compared with WT mice. More neutrophils were recruited in the lesions in MR1-/- mice than in WT mice. WT mice contained fewer MAIT cells in their skin lesions following elicitation with DNFB, and MR1-/- mice lacking MAIT cells exhibited a significant increase in IL-17-producing αβ and γδ T cells in the skin. Collectively, MR1-/- mice displayed exacerbated ACD from an early phase with an enhanced type 3 immune response, although the precise mechanism of this enhancement remains elusive.

Antibiotic use in early life subsequently impairs MAIT cell-mediated immunity

“…Antibiotic use during infancy has been shown to increase the risk of atopic dermatitis in children, 8 although it remains unclear whether MAIT cells are beneficial or detrimental during this inflammatory skin disease. 54,55…”

“…Antibiotic use during infancy has been shown to increase the risk of atopic dermatitis in children, 8 although it remains unclear whether MAIT cells are beneficial or detrimental during this inflammatory skin disease. 54,55 To maintain the riboflavin synthesis capacity of the microbiome during antibiotic treatment, we administered a human fecal isolate of B. thetaiotaomicron, which was sufficient to increase MAIT cell abundance and restore respiratory immunity. Due to the abundance of Bacteroidaceae within the intestinal microbiota of infants, 35 members of this bacterial family may be essential for MAIT cell development.…”