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Ccr6 Deficiency attenuates spontaneous chronic colitis in Winnie

Citation

Ranasinghe, R and Fernando, R and Perera, AP and Shastri, M and Basheer, W and Scowen, P and Pinfold, T and Eri, R, Ccr6 Deficiency attenuates spontaneous chronic colitis in Winnie, Gastrointestinal Disorders, 2 pp. 27-47. ISSN 2624-5647 (2020) [Refereed Article]


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Copyright 2020 the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license http://creativecommons.org/licenses/by/4.0/).

DOI: doi:10.3390/gidisord2010004

Abstract

Background: The immune‐modulator behaviour of the CCR6/CCL20 axis in multi ‐system pathophysiology and molecular signalling was investigated at two clinically significant time points, using a Ccr6ódeficient mouse model of spontaneous colitis.

Methods:Four groups of mice, (C57BL/6J, Ccr6−/− of C57BL/6J, Winnie ◊Ccr6−/−and Winnie) were utilized and (I) colonic clinical parameters (2) histology of colon, spleen, kidney and liver (3) T and B lymphocyte distribution in the spleen and MLN by flowcytometry (5) colonic CCL20, phosphorylated PI3K and phosphorylated Akt expression by immunohistochemistry and (6) colonic cytokine expression by RT‐PCR were evaluated.

Results: deficiency was shown to attenuate inflammation in the spleen, liver and gut while renal histology remained unaffected. Marked focal lobular inflammation with reactive nuclear features were observed in hepatocytes and a significant neutrophil infiltration in red pulp with extra medullary hemopoiesis in the spleen existed in Winnie. These changes were considerably reduced in Winnie ◊Ccr6−/−‐ with elevated goblet cell numbers and mucus production in the colonic epithelium.

Conclusions: Results indicate that Ccr6‐ deficiency in the colitis model contributes towards resolution of disease. Our findings demonstrate an intricate networking role for CCR6 in immune activation, which is downregulated by Ccr6 deficiency, and could provide newer clinical therapies in colitis.

Item Details

Item Type:Refereed Article
Keywords:CCR6, colitis, Winnie, multi‐system pathophysiology, molecular signalling, inflammation, immunity
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Ranasinghe, R (Ms Hewausaramba Ranasinghe)
UTAS Author:Perera, AP (Mrs Agampodi Perera)
UTAS Author:Shastri, M (Mr Madhur Shastri)
UTAS Author:Basheer, W (Dr Waheedha Basheer)
UTAS Author:Scowen, P (Mr Paul Scowen)
UTAS Author:Pinfold, T (Dr Terry Pinfold)
UTAS Author:Eri, R (Associate Professor Raj Eri)
ID Code:137536
Year Published:2020
Deposited By:Health Sciences
Deposited On:2020-02-19
Last Modified:2021-06-23
Downloads:0

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