Intensified Th9 Response is Associated with the Immunopathogenesis of Active Ulcerative Colitis

ABSTRACT

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine histologically characterized by indistinct sustained inflammatory responses. Genetical susceptibility and environmental factors’ effects play the roles in disease occurrence and it can be life threatening if remains untreated. It seems that intensification of inflammatory responses in this condition is not restricted to a specific cell line of T lymphocytes. Our aim was to determine the number of T helper 9 (Th9) cells in inflamed colonic biopsies of UC patients. We also correlated it with interleukin (IL)-9 protein level in addition to certain genes expressions associated with Th9 phenotype.

Methods: Expression of CD4 and IL-9 were evaluated by immunohistochemical staining. Enzyme linked immunosorbent assay (ELISA) was performed to determine the colonic expression of IL-9 protein and finally mRNA expressions of interferon regulatory factor 4 (Irf4), Smad2, and Smad3 were measured by real-time polymerase chain reaction (RT-PCR) as critical transcription factors of Th9 differentiation.

Results: Number of Th9 cells was significantly increased in inflamed samples as compared with normal tissues. Also quantitative measurement of IL-9 by ELISA and mRNA expressions of Irf4, Smad2, and Smad3 showed notable correlative enhancements in patient’s samples.

Conclusion: Function and number of Th9 cells are up-regulated in the inflamed mucosa of UC patients as with the protein secretion of IL-9 and mRNA expressions of Irf4, Smad2, and Smad3, so Th9 cells and IL-9 may become remarkable therapeutic targets for IBD treatment in the future.

KEYWORDS:

• Interleukin 9
• Irf4
• Smads
• Th9
• Ulcerative colitis

Acknowledgment

The creators are appreciative to the staffs of Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran, and also to the staffs of Cellular and Molecular Research Center, Shahrekord University of Medical Sciences and the specialists of the endoscopy unit of Shahrekord Hajar Hospital for their participation.

Ethical approval

The research additionally was approved by the ethical board of Shahrekord University of medical sciences with number: IR.SKUMS.REC.1395.313.

Competing interests

None declared.

Additional information

Funding

The funding was provided by research deputy of Shahrekord University of Medial Sciences with grant number: 1395–01-74–3214.