Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.

Colitis and Colorectal Carcinogenesis: The Focus on Isolated Lymphoid Follicles

“…As a result, while ILCs are the innate counterparts of T cells, they lack T-cell receptors produced by somatic recombination of antigen-specific receptors. ILCs respond quickly to signals or cytokines produced by other cells, allowing them to act early in the immune response [ 19 ]. Other distinguishing features of ILCs from lymphocytes include the fact that, unlike intestinal B, T, and NK cells, their intestinal population is not constantly replaced from the circulation, and the ILCs constantly produce their representative cytokines at a steady rate, in contrast to T cells’ on-demand production [ 19 , 20 ].…”

“…Anomalies in the ILC population balance disrupt intestinal homeostasis, resulting in gut inflammation. The balance of ILC1s and ILC3s is closely linked to IBD and gut inflammation [ 19 ].…”

“…This rise is accompanied by a decrease in natural cytotoxicity receptor (NCR) + ILC3s, which worsens the disease. In the lamina propria of inflamed tissues from CD patients, the ILC population is skewed toward the CD127 + ILC1 subset [ 19 , 63 ]. In response to IL-12 and IL-18, these CD127+ ILC1s produce a large amount of IFN-γ [ 19 ].…”

“…In the lamina propria of inflamed tissues from CD patients, the ILC population is skewed toward the CD127 + ILC1 subset [ 19 , 63 ]. In response to IL-12 and IL-18, these CD127+ ILC1s produce a large amount of IFN-γ [ 19 ].…”

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

“…They are generally classified in three types, with type 1 ILCs including NK cells. A large body of evidence demonstrates their role in IBD pathophysiology [ 203 ]. In line with this, patients with Crohn’s disease have increased numbers of NK cells in the small intestinal epithelial compartment [ 204 ] and colonic lamina propria [ 205 ].…”