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Ccr6 Deficiency attenuates spontaneous chronic colitis in Winnie

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posted on 2023-05-20, 11:05 authored by Ranasinghe, R, Fernando, R, Perera, AP, Madhur ShastriMadhur Shastri, Basheer, W, Paul ScowenPaul Scowen, Terry PinfoldTerry Pinfold, Rajaraman Eri

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 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 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.

History

Publication title

Gastrointestinal Disorders

Pagination

27-47

ISSN

2624-5647

Department/School

School of Health Sciences

Publisher

M D P I AG

Place of publication

Switzerland

Rights statement

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/).

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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