The Role of CD1d and MR1 Restricted T Cells in the Liver

Abstract

The liver is one of the most important immunological organs that remains tolerogenic in homeostasis yet promotes rapid responses to pathogens in the presence of a systemic infection. The composition of leucocytes in the liver is highly distinct from that of the blood and other lymphoid organs, particularly with respect to enrichment of innate T cells, i.e., invariant NKT cells (iNKT cells) and Mucosal-Associated Invariant T cells (MAIT cells). In recent years, studies have revealed insights into their biology and potential roles in maintaining the immune-environment in the liver. As the primary liver-resident immune cells, they are emerging as significant players in the human immune system and are associated with an increasing number of clinical diseases. As such, innate T cells are promising targets for modifying host defense and inflammation of various liver diseases, including viral, autoimmune, and those of tumor origin. In this review, we emphasize and discuss some of the recent discoveries and advances in the biology of innate T cells, their recruitment and diversity in the liver, and their role in various liver diseases, postulating on their potential application in immunotherapy.

Codelivery of mRNA with α-Galactosylceramide Using a New Lipopolyplex Formulation Induces a Strong Antitumor Response upon Intravenous Administration

“…Conventionally, liver accumulation of drug-loaded nanoparticles is strongly unwanted, and it is unanimously recognized as the major barrier to clinical translation of nanomaterials. However, in this study, liver accumulation could be desirable, given that our strategy involves the delivery of two distinct immune agents, α-GalCer and an mRNA coding for a selected tumor antigen, that are recognized by iNKT (most abundant in the liver) and T cells (most abundant in lymphoid organs), respectively . Bioluminescence distribution revealed efficient dual targeting of the liver and lymphoid organs (mostly spleen, ILNs, and MLNs) and excluded any undesired off-target signal.…”

Covering All the Bases: Complementary MR1 Antigen Presentation Pathways Sample Diverse Antigens and Intracellular Compartments

“…While MR1 has been consistently found to localize to the ER, it has also been reported to co-localize with late endosomal proteins ( 30 , 36 , 37 ). We have observed a vesicular distribution of MR1 even in the absence of exogenously provided ligands ( 36 ), indicating that constitutive egress from the ER is possible.…”

Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury

“…The nature of the antigens that would stimulate iNKT cells is complex. In fact, mouse and human iNKT cells can recognize lipid and glycolipid antigens of self or microbial origin presented on MHC class-I-like CD1d molecules [ 48 , 49 ]. In this sense, intestinal permeability appears to be increased in NAFLD patients, which would allow a constant exposure to dietary and microbial antigens.…”