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Ccr6 Deficiency attenuates spontaneous chronic colitis in Winnie


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Ranasinghe, R, Fernando, R, Perera, AP, Shastri, M ORCID: 0000-0002-1012-2779, Basheer, W, Scowen, P, Pinfold, T ORCID: 0000-0002-0506-6389 and Eri, R ORCID: 0000-0003-1688-8043 2020 , 'Ccr6 Deficiency attenuates spontaneous chronic colitis in Winnie' , Gastrointestinal Disorders, vol. 2 , pp. 27-47 , doi: 10.3390/gidisord2010004.

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Background: The immune‐modulator behaviour of the CCR6/CCL20 axis in multi ‐systempathophysiology and molecular signalling was investigated at two clinically significant time points,using a Ccr6—deficient 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 clinicalparameters (2) histology of colon, spleen, kidney and liver (3) T and B lymphocyte distribution inthe spleen and MLN by flowcytometry (5) colonic CCL20, phosphorylated PI3K andphosphorylated Akt expression by immunohistochemistry and (6) colonic cytokine expression byRT‐PCR were evaluated. Results: deficiency was shown to attenuate inflammation in thespleen, liver and gut while renal histology remained unaffected. Marked focal lobular inflammationwith reactive nuclear features were observed in hepatocytes and a significant neutrophil infiltrationin red pulp with extra medullary hemopoiesis in the spleen existed in Winnie. These changes wereconsiderably reduced in Winnie ×Ccr6−/−‐ with elevated goblet cell numbers and mucus productionin the colonic epithelium. Conclusions: Results indicate that Ccr6‐ deficiency in the colitis modelcontributes towards resolution of disease. Our findings demonstrate an intricate networking rolefor CCR6 in immune activation, which is downregulated by Ccr6 deficiency, and could providenewer clinical therapies in colitis.

Item Type: Article
Authors/Creators:Ranasinghe, R and Fernando, R and Perera, AP and Shastri, M and Basheer, W and Scowen, P and Pinfold, T and Eri, R
Keywords: CCR6, colitis, Winnie, multi‐system pathophysiology, molecular signalling, inflammation, immunity
Journal or Publication Title: Gastrointestinal Disorders
Publisher: M D P I AG
ISSN: 2624-5647
DOI / ID Number: 10.3390/gidisord2010004
Copyright Information:

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

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