Document Type : Original Article
Authors
- Seyed Mohammad Javadzadeh 1
- Mohsen Keykhosravi 1
- Mohsen Tehrani 1, 2
- Hossein Asgarian-Omran 1, 2, 3
- Mohsen Rashidi 4
- Hadi Hossein-Nattaj 1
- Laleh Vahedi-Larijani 5
- Abolghasem Ajami 1, 6, 7
1 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2 Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
3 Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran
4 Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
5 Department of Pathology, Mazandaran University of Medical Sciences, Sari, Iran
6 Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
7 Antimicrobial Resistance Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Abstract
Background: Innate Lymphoid Cells (ILCs) promote tissue homeostasis, contribute to the immune defense mechanisms, and play important roles in the initiation of immune responses and chronic inflammation.
Objective: To understand the roles of innate lymphoid cells in the pathophysiology of colorectal cancer (CRC) in the mouse model.
Methods: CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) in Balb/c mice (the chemically induced group=18 mice), or orthotopic injection of CT-26 cell line into the colon of another set of Balb/c mice (the orthotopic group=14mice). Normal saline was injected into 18 mice, as the sham group. After 80 days, the chemically induced group was divided into two subgroups, dysplasia (8 mice) and reparative change (10 mice), based on pathological examinations. The frequencies of ILC1, 2, and 3 were then measured in colon tissues using flow cytometry by four markers including an anti-mouse lineage cocktail (FITC anti-mCD3/FITC anti-mGr-1/FITC anti-mCD11b/ FITC anti-mCD45R (B220)/FITC anti-mTer-119), PE/Cy7 anti-mouse CD45, PE anti-mouse CD117 (c-kit), and APC anti-mouse IL-33 Rα (ST2).
Results: The total ILC population was significantly higher in the chemically induced reparative change compared with the sham group. ILC1 percentage in the chemically induced reparative change was significantly higher compared to those in the other three groups (Sham, chemically induced dysplasia and orthotopic dysplasia). The orthotopic dysplasia group showed more ILC3 percentage than the other groups.
Conclusion: ILC1 and ILC3 subgroups increased significantly in reparative and dysplastic experimental CRC respectively. Thus ILC1 may have an inhibitory effect on tumor growth whereas ILC3 promotes tumor progression.
Keywords
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