Intest Res.  2012 Oct;10(4):317-323. 10.5217/ir.2012.10.4.317.

Immunological Abnormalities in the Pathogenesis of Inflammatory Bowel Disease

• Hisamatsu
• Mikami Y
• Matsuoka K
• Kanai T
• Hibi T

• KMID: 2174247
• DOI: http://doi.org/10.5217/ir.2012.10.4.317

Abstract

Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-alpha. In addition, the CD14+ macrophages contributed to interferon (IFN)-gamma production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-gamma-positive feedback loop in IBD patients. We also discuss IFN-gamma and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)gammat, the master regulator of Th 17 cells, and are differentiated 'alternative Th 1 cells.' In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-gamma. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD.

Keyword

Macrophage; TNFalpha; IL-23; Mucosal NK cell; Th17

MeSH Terms

Antigen-Presenting Cells
Bacteria
Child
Child, Orphaned
Colitis
Colitis, Ulcerative
Crohn Disease
Cytokines
Dendritic Cells
Epithelial Cells
Homeostasis
Humans
Inflammatory Bowel Diseases
Interferons
Interleukin-17
Interleukin-23
Interleukins
Intestines
Killer Cells, Natural
Lymphocytes
Macrophages
Mucous Membrane
Plastics
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
Tumor Necrosis Factor-alpha
Cytokines
Interferons
Interleukin-17
Interleukin-23
Interleukins
Plastics
Tumor Necrosis Factor-alpha