ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis

Abstract

Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.

Multiple sclerosis and inflammatory bowel disease: A systematic review and meta‐analysis

“… 30 The gut microenvironment was found to have the ability to modulate the activation and differentiation of autoreactive T cells and guide them to the CNS. 37 …”

Lactoferrin modulates gut microbiota and Toll-like receptors (TLRs) in mice with dysbiosis induced by antibiotics

“…These cells are well known for their ability to maintain the integrity of the intestinal barrier and to shape the immune response to gut microbiota through an IL-22-dependent pathway. 10,11 All these changes alter immune homeostasis in the gut and make the host more susceptible to the overgrowth of opportunistic pathogens and intestinal infections.…”

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

“…Changes in the composition of the gut microbiota are closely related to changes in the levels of inflammatory factors, for example, the levels of GM-CSF, IL-12p70, IL-15, IL-1RA, IL-9, IL-23 and TNF-a increased, and the levels of IL-10 decreased in ICH patients. This study indicated that an increase in Enterococcus and a decrease in Prevotella increased the risk of ICH [43]. Thus, the diversity of the gut microbiota decreased after ICH, as some phyla and genera increased in abundance, and some decreased.…”

“…However, in the late stages of ICH, dendritic cells in the mesenteric lymph nodes promote the migration of Treg cells to the intestine, thereby inhibiting the differentiation of IL-17-producing γδ T cells and attenuating the migration of γδ T cells from the gut to the brain and ultimately protecting against cerebral ischemia/reperfusion injury [45]. the levels of GM-CSF, IL-12p70, IL-15, IL-1RA, IL-9, IL-23 and TNF-a increased, and the levels of IL-10 decreased [43] In addition, gut bacteria generate neuroactive compounds and mediate neuronal functions, thus affecting the behavior after ICH. Previous research demonstrated that the gut microbiota affects the host homeostasis through bile acid metabolism, amino acid metabolism and metabolic pathways such as those involving SCFAs.…”