Intestinal Immune Imbalance is an Alarm in the Development of IBD

Abstract

Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is a chronic relapse bowel disease with an increasing incidence worldwide. Clinical treatments for IBD are limited and inefficient. However, the pathogenesis of immune-mediated IBD remains unclear. This review describes the activation of innate and adaptive immune functions by intestinal immune cells to regulate intestinal immune balance and maintain intestinal mucosal integrity. Changes in susceptible genes, autophagy, energy metabolism, and other factors interact in a complex manner with the immune system, eventually leading to intestinal immune imbalance and the onset of IBD. These events indicate that intestinal immune imbalance is an alarm for IBD development, further opening new possibilities for the unprecedented development of immunotherapy for IBD.

Figure 1

The factors of the innate immune system, adaptive immune system, genetic alterations, impaired autophagy, imbalance of energy metabolism (such as lipid metabolism, glucose metabolism, and amino acid metabolism), and electrolyte disorders interact in complex manners, which ultimately cause intestinal immune imbalance and trigger the onset of IBD. The red font indicates upregulation, while the blue font indicates downregulation. Abbreviations: ILCs, innate lymphocytes; NKT, natural killer T; IEC, intestinal epithelial cell; MIP3, macrophage inflammatory protein 3; NOD2, nucleotide-binding and oligomerization domain 2; Phox2b, paired-like homeobox 2b; Atg16l1, autophagy-related 16-like 1; XIAP, X-linked inhibitor of apoptosis; NPC1, Niemann–Pick disease type C1; MTMR3, myotubularin-related protein 3; IRGM, immunity-related GTPase M; GPR65, G-protein coupled receptor 65; PUFAs, polyunsaturated fatty acids; PPARγ, peroxisome proliferator-activated receptor γ; SCFAs, short-chain fatty acids; G6PC3, glucose-6-phosphatase catalytic subunit 3; DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide 1; AhR, aryl hydrocarbon receptor.