Intest Res.  2018 Jan;16(1):26-42. 10.5217/ir.2018.16.1.26.

Immunological pathogenesis of inflammatory bowel disease

• Lee SH
• Kwon JE
• Cho ML

• KMID: 2402644
• DOI: http://doi.org/10.5217/ir.2018.16.1.26

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17) cells and innate lymphoid cells (ILCs) are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

Keyword

Inflammatory bowel disease; Th17 cells; Innate lymphoid cells

MeSH Terms

Colitis
Colitis, Ulcerative
Crohn Disease
Gastrointestinal Microbiome
Gastrointestinal Tract
Genetics, Microbial
Humans
Immunologic Factors
Inflammatory Bowel Diseases*
Lymphocytes
Plastics
Th17 Cells
Immunologic Factors
Plastics

Figure

• 

  Fig. 1 Histology of colon tissue from IBD patients. (A) H&E of colon tissue from UC and CD patients (H&E, ×40). (B, C) Signal transducer and activator of transcription 3 (STAT3) and interleukin 17 (IL-17) expression in colon tissue from UC and CD patients (immunohistochemistry, ×200).

• 

  Fig. 2 Pathogenic innate lymphoid cells (ILCs) and T cells in mucosal cells from IBD patients. ILCs have common properties with T effector cells. Lineage-specific transcription factors expressing ILCs or a subset of T cells produce the same cytokine. Natural cytotoxicity receptor (NCR)-expressing ILCs are classified differently from T cells. T-bet, T-box expressed in T cells; IFN, interferon; TNF, tumor necrosis factor; IL, interleukin; RORγt, retinoic acid receptor-related orphan receptor γt.

• 

  Fig. 3 Present IBD therapeutic strategies that involve prevention of T cell and innate lymphoid cells (ILC) production or their inhibition. T cells and ILCs have a common therapeutic target. Compared with classical IBD therapeutic agents, new therapeutic strategies may involve T cells; ILCs such as interleukin (IL)-23 and IL-12-, tumor necrosis factor (TNF)-, and integrin-targeting agents; and signal transducer and activator of transcription (STAT) inhibitors. NF, nuclear factor; AP-1, activator protein 1; cAMP, cyclic adenosine 3′:5′-monophosphate.

• 

  Fig. 4 Reciprocal balance for intestinal immune homeostasis and inflammation. The normal state is mediated by a reciprocal balance between immune cells (Treg and Breg vs. Th17 and ILC1) and cytokines that are secreted to maintain the conditions in the intestine. However, an imbalance in immune cells leads to the destruction of intestinal epithelial cells and the invasion of commensal microbiota. This situation leads to the uncontrolled release of cytokines, which is a key event in the pathogenesis of IBD. Treg, regulatory T; Breg, regulatory B; ILC, innate lymphoid cells; DC, dendritic cell; IL, interleukin; NKT, natural killer T; Th17, T helper 17.

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