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.
Highlights
Inflammatory bowel disease (IBD) originates from an interplay between the environment, gut microbiota and immunological factors in genetically susceptible individuals, which promotes intestinal barrier dysfunction, tissue damage and dysregulated innate and adaptive immune responses [5,11,12] (Figure 1)
Epithelial fucose is used as a dietary carbohydrate by commensal bacteria, establishing a mechanism of host-microbiota symbiosis that contributes to intestinal homeostasis [167,168]
In an anti-CD4 and anti-CD90 antibody-depleting mouse colitis model, IL-6 was found to contribute to the activation and production of IL-17A, IL-22 and IFN-γ in intestinal ILC3s, a finding confirmed in isolated lamina propria cells from IBD patients [119]
Summary
IBD originates from an interplay between the environment, gut microbiota and immunological factors in genetically susceptible individuals, which promotes intestinal barrier dysfunction, tissue damage and dysregulated innate and adaptive immune responses [5,11,12] (Figure 1). The predominant gut-infiltrating proinflammatory T cell populations in IBD are Th1 cells, which express the transcription factor T-bet and the cytokine interferon (IFN-)γ, and Th17 cells, which express the transcription factor retinoid (RAR)-related orphan receptor (ROR)γt and the cytokine IL-17 [29,30,31,32,33,34] Infiltration by these populations is accompanied by an increase in the numbers of GATA-3-expressing IL-5- and IL-13-producing Th2 cells [35,36] and insufficient numbers of immune-suppressing cells, such as Foxp3-expressing T regulatory (Treg) and T regulatory type 1 (Tr1) cells [37,38,39] (Figure 2). ILCs play important roles in antimicrobial defense, and contribute to organ development, tissue protection and regeneration and mucosal homeostasis [49,50] These cells belong to the innate immune response but originate from the same common lymphoid progenitor as lymphocytes [51,52]. ILC1s are broadly noncytotoxic but produce IFN-γ in response to IL-12 and tumor necrosis factor (TNF) to target intracellular pathogens such as viruses and bacteria [84,85,86,87,88]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
