Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

Abstract

Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.

Number and function of circulatory helper innate lymphoid cells are unaffected by immunosuppressive drugs used in solid organ recipients – a single centre cohort study

“…Interestingly, an ILC2‐mediated induction of a type 2 response has been shown to protect kidneys from damage both in models of ischemic acute kidney injury or chronic proteinuric disease . Intrahepatic hILC are better characterized, and pivotal roles of hILC subsets in liver inflammation, cancer, or fibrosis have been described . Among hILC in healthy human livers, NKp44‐ ILC3 is the most prominent subset, but increased ILC2 have been associated with human liver fibrosis .…”

Role of the immune system in liver transplantation and its implications for therapeutic interventions

“…The liver's innate immune cell repertoire encompasses neutrophils, iNKT cells, mucosal‐associated invariant T (MAIT) cells, γδT cells, and innate lymphoid cells (ILCs). 68 , 69 , 70 , 71 Neutrophils serve a diverse array of functions, which include triggering early inflammatory responses, phagocyte fragmentation, inducing macrophage phenotypic changes, and facilitating vascular regeneration. 72 , 73 , 74 , 75 iNKT cells are recognized for their roles in inflammation, tumorigenesis, and allergic reactions.…”

Innate Lymphoid Cells in the Malignant Melanoma Microenvironment

“…Hepatic Type 1 ILCs are involved in immune regulation with opposing roles, either favoring or inhibiting an effective local immune response [53,54]. Liver ILC1s, previously identified as liver-resident NK cells, reside in the organ in a state of equilibrium [55] and, unlike conventional NK cells, express TNF-related apoptosis-inducing ligand (TRAIL) [56,57].…”

“…Type 2 and 3 ILCs represent about 5% of all the ILCs in a healthy liver (Figure 3). ILCs deregulation may lead to a wide range of liver disorders [54]. The activation and expansion of Type NK cells produce perforin and granzyme B, which endow these cells with robust cytotoxic activity [44].…”

“…Type 2 and 3 ILCs represent about 5% of all the ILCs in a healthy liver (Figure 3). ILCs deregulation may lead to a wide range of liver disorders [54]. The activation and expansion of Type 2 and 3 ILCs in chronic hepatocellular stress or ischemia/reperfusion injury [51] may counteract injury and increase the levels of IL-22, a survival factor for hepatocytes [58].…”