MAIT cells: new guardians of the liver

Abstract

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases.

Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment

“…The MAIT cells are specifically enriched in the liver and involved in the antibacterial response. They have an invariant TCR (TCRVα7.2) and express the C‐lectin CD161 . In our work, the frequency of these cells was decreased in the blood of AIH patients, and the immunohistochemistry study of liver biopsies showed an increased density of TCRVα7.2‐ and CD161‐positive cells, suggesting their recruitment to the site of inflammation.…”

IL‐17 polarization of MAIT cells is derived from the activation of two different pathways

“…MAIT cells were analyzed by flow cytometry and RT-PCR and isolated from PBMCs and salivary glands mononuclear cells (as previously described) [5] of patients and controls by FACSAria cell sorter. Since the majority of MAIT cells are CD8 + cells [6], with very low frequencies of double negative CD4/CD8 MAIT cells, we confined our analysis to the CD8 + fraction. According to Banovic and colleagues, flow cytometry analyses showed a significant reduction of MAIT cells in the peripheral blood (Fig.…”

The MAIT conundrum – how human MAIT cells distinguish bacterial colonization from infection in mucosal barrier tissues

“…Expression of cytotoxic and regulatory T-cell molecule (CRTAM), which controls residency of T-cells in the gut[73], is also enhanced in MAIT cells isolated from tissues[44], supporting the notion that a resident population is plausible. In addition, MAIT cell frequencies in the blood are diminished in context of various infections and autoimmune diseases, sometimes irreversibly, which could be explained if cells are retained within tissues [1–11]. …”

“…Changes in MAIT cell frequency and phenotype have been reported in numerous disease settings including acute and chronic infections as well as autoimmune and malignant disorders. Recent reviews provide a comprehensive overview of these clinical studies as well as key aspects of MAIT cell function including antigen recognition, antimicrobial properties and their putative role in the liver[1–11]. Here we provide an overview of the recent human MAIT cell literature to address how a cell that recognizes bacterially-derived antigen and is found in mucosal barrier tissues colonized by commensal bacteria, avoids responding to these commensal-derived antigens while maintaining responsiveness to bacterial infections.…”