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Type 1 T-helper cell predominance in granulomas of Crohn's disease
T Kakazu1, J Hara, T Matsumoto
1Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan.
Insights
Crohn's disease (CD) granulomas show type 1 T-helper responses, involving interferon-gamma and interleukin-12. These findings suggest a role for type 1 T-helper cells in CD pathogenesis.
Area of Science:
- Gastroenterology
- Immunology
- Pathology
Background:
- Crohn's disease (CD) pathogenesis is linked to cytokine production, particularly type-1 cytokines.
- Understanding in situ cytokine profiles is crucial for elucidating CD mechanisms.
- Noncaseating granulomas are a hallmark of CD and warrant specific investigation.
Purpose of the Study:
- To localize cytokine-containing cells in Crohn's disease (CD) tissue using immunohistochemistry.
- To investigate the cytokine profiles within noncaseating granulomas in CD.
- To compare the cytokine expression in CD with that observed in ulcerative colitis (UC).
Main Methods:
- Utilized the biotin-streptavidin-peroxidase method on surgical frozen sections.
- Performed immunohistochemical analysis for interferon-gamma, interleukin-2, -4, -10, and -12.
- Examined cytokine expression in normal colonic tissue, inflamed CD tissue, CD granulomas, and inflamed UC tissue.
Main Results:
- Normal colonic tissue showed rare cytokine expression, except for interleukin-4.
- Actively inflamed CD tissue exhibited increased expression of all examined cytokines by mononuclear cells.
- CD granulomas were characterized by interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells, with limited interleukin-4 or -10.
- Compared to UC, CD tissue showed higher interferon-gamma and interleukin-12 expression and lower interleukin-10, indicating a predominant type 1 T-helper cell response in CD.
Conclusions:
- Granulomas in Crohn's disease are associated with type 1 T-helper responses.
- These type 1 T-helper responses likely contribute to the pathogenesis of Crohn's disease.
- The distinct cytokine profile in CD suggests a specific immune response driving the disease process.
Objective:
The pathogenesis of Crohn's disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC).
Methods:
We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12).
Results:
In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC.
Conclusions:
The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.