Mucosal-Associated Invariant T cell in liver diseases

Abstract

Mucosal-associated invariant T cells (MAIT cells) are a new population of innate immune cells, which are abundant in the liver and play complex roles in various liver diseases. In this review, we summarize MAIT cells in the liver diseases in recent studies, figure out the role of MAIT cells in various liver disease, including Alcoholic liver disease, Non-alcoholic liver disease, Autoimmune liver diseases, Viral hepatitis and Liver Cancer. Briefly, MAIT cells are involved in anti-bacteria responses in the alcoholic liver diseases. Besides, the activated MAIT cells promote the liver inflammation by secreting inflammatory cytokines and produce regulatory cytokines, which induces anti-inflammatory macrophage polarization. MAIT cells participate in the liver fibrosis via enhancing hepatic stellate cell activation. In viral hepatitis, MAIT cells exhibit a flawed and exhausted phenotype, which results in little effect on controlling the virus and bacteria. In liver cancer, MAIT cells indicate the disease progression and the outcome of therapy. In summary, MAIT cells are attractive biomarkers and therapeutic targets for liver disease.

Keywords: MAIT cells; alcoholic liver disease; autoimmune liver disease; liver cancer; non-alcoholic liver disease.

Figure 1

The characteristics of MAIT cell. MAIT cells are defined as CD3⁺CD161⁺Vα7.2⁺ lymphocytes. Most MAIT cells are CD8⁺T subset. The MR1-5-OP-RU and TCRβ can define MAIT cells. MAIT cells possess homing receptors CCR6, CXCR6, β7-integrins and CXCR3 to migrate to the liver, intestines and some inflammatory tissues. MAIT cells express cytokine receptors IL-12R and IL-18R, which can be activated by different cytokines. Meanwhile, MAIT cells have the multidrug resistance transporter (ABCB1). Once being activated, MAIT cells produce Th1 and Th17 cytokines, such as TNF-α,IFN-γ,IL-17. Meanwhile MAIT cells release granzyme B and perforin to kill the infected cells. This picture was adapted from the reference .

Figure 2

MAIT cells in different liver diseases. In alcoholic liver disease, gut bacterial directly affect the function of MAIT cells. In nonalcoholic fatty liver disease, FFA stimulates Kupffer cells, which activates MAIT cells to produce IL-4. As a result, activated MAIT cells promote macrophage to polarize. In autoimmune liver disease, MAIT cells are a profibrogenic and proinflammatory cell population. In viral liver disease, MAIT cells exhibit cell exhaustion and impaired effector function. In liver cancer, MAIT cells show activated and exhausted phenotype. Meanwhile, MAIT cells enhance the progression of cancer. This picture was adapted from the reference .