Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

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Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity. / Trivedi, Palak J; Bruns, Tony; Ward, Stephen; Mai, Martina; Schmidt, Carsten; Hirschfield, Gideon M; Weston, Chris J; Adams, David H.

In: Journal of Autoimmunity, Vol. 68, 04.2016, p. 98–104.

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@article{472783b4f391498fa4d24ad1db9b52cb,
title = "Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity",
abstract = "CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4(+)) and 30% (CD8(+)) of tissue-infiltrating T-cells in colitis were identified as CCR9(+) effector lymphocytes, compared to <10% of T-cells being CCR9(+) in normal colon. Sorted CCR9(+) lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9(-) counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver.",
author = "Trivedi, {Palak J} and Tony Bruns and Stephen Ward and Martina Mai and Carsten Schmidt and Hirschfield, {Gideon M} and Weston, {Chris J} and Adams, {David H}",
note = "Copyright {\textcopyright} 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.",
year = "2016",
month = apr,
doi = "10.1016/j.jaut.2016.01.001",
language = "English",
volume = "68",
pages = "98–104",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity

AU - Trivedi, Palak J

AU - Bruns, Tony

AU - Ward, Stephen

AU - Mai, Martina

AU - Schmidt, Carsten

AU - Hirschfield, Gideon M

AU - Weston, Chris J

AU - Adams, David H

N1 - Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2016/4

Y1 - 2016/4

N2 - CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4(+)) and 30% (CD8(+)) of tissue-infiltrating T-cells in colitis were identified as CCR9(+) effector lymphocytes, compared to <10% of T-cells being CCR9(+) in normal colon. Sorted CCR9(+) lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9(-) counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver.

AB - CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFα expression. Moreover, approximately 90% (CD4(+)) and 30% (CD8(+)) of tissue-infiltrating T-cells in colitis were identified as CCR9(+) effector lymphocytes, compared to <10% of T-cells being CCR9(+) in normal colon. Sorted CCR9(+) lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9(-) counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver.

U2 - 10.1016/j.jaut.2016.01.001

DO - 10.1016/j.jaut.2016.01.001

M3 - Article

C2 - 26873648

VL - 68

SP - 98

EP - 104

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -