The Immunological Basis of Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBDs) are chronic ailments, Crohn's disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

Figure 1

Intestinal epithelial barrier and the immune system in inflammatory bowel disease. Ag: antigen; APC: antigen presenting cells; IL: interleukin; IFN-γ: interferon gamma; IgA: immunoglobulin A; M cell: microfold cell; TGF-β: transforming growth factor beta; TGF-α: transforming growth factor-alpha; Th: T helper cell; Treg: regulatory T cells; TNF: tumor necrosis factor.

Figure 2

Toll-like receptor signaling pathways. LPS: lipopolysaccharide; CD14: cluster of differentiation 14; MD-2: lymphocyte antigen 96; TLR: toll-like receptor; TRIF: TIR domain-containing adaptor-inducing IFN-β; TRAM: TRIF-related adaptor molecule; TRAP: tartrate-resistant acid phosphatase; MyD88: myeloid differentiation primary response 88; IRAK4: interleukin-1 receptor-associated kinase 4; IRAKM: interleukin-1 receptor-associated kinase M; IRAK1: interleukin-1 receptor-associated kinase 1; IRAK2: interleukin-1 receptor-associated kinase 2; TOLLIP: toll interacting protein; FADD: Fas-associated protein with death domain; Caspase-8: cysteine-aspartic protease 8; TIRAP: toll-interleukin-1 receptor domain-containing adaptor protein; UBC13: ubiquitin-conjugating enzyme; TRAF6: TNF receptor-associated factor 6; UEV1A: ubiquitin-conjugating enzyme E2 variant 1A; ECSIT: evolutionarily conserved signaling intermediate In toll pathway; IKKγ: nuclear factor kappa-B kinase subunit gamma; IKKβ: nuclear factor kappa-B kinase subunit beta; NEMO: NF-kappa-B essential modulator; IKKα: nuclear factor kappa-B kinase subunit alpha; TK1: thymidine kinase 1; TAB1: TGF-beta activated kinase 1; MKK4/7: mitogen-activated protein kinase kinases 4; JNK: Janus kinase; ub: ubiquinization; ICBα: inhibitor of kappa-B; p65/RELA: nuclear factor NF-kappa-B P65 subunit; NF-kB: nuclear factor kappa-B; IL: interleukin; TNF-α: tumor necrosis factor-alpha.