A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.

Chemokines are small proteins that promote leukocyte migration during development, infection, and inflammation. We and others isolated the unique chemokine CCL21, a potent chemo-attractant for naïve T-cells, naïve B-cells, and immature dendritic cells. CCL21 has a 37 amino acid carboxy terminal exte...

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Autores principales:	Maegan L Capitano, Aruna Jaiswal, Hal E Broxmeyer, Yilianys Pride, Sarah Glover, Fatemah G Amlashi, Austin Kirby, Gayathri Srinivasan, Elizabeth A Williamson, Daniel Mais, Robert Hromas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ea93e54ea7d4c8bb8880efa6b63ef0d
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spelling	oai:doaj.org-article:1ea93e54ea7d4c8bb8880efa6b63ef0d2021-12-02T20:05:14ZA humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.1932-620310.1371/journal.pone.0252805https://doaj.org/article/1ea93e54ea7d4c8bb8880efa6b63ef0d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252805https://doaj.org/toc/1932-6203Chemokines are small proteins that promote leukocyte migration during development, infection, and inflammation. We and others isolated the unique chemokine CCL21, a potent chemo-attractant for naïve T-cells, naïve B-cells, and immature dendritic cells. CCL21 has a 37 amino acid carboxy terminal extension that is distinct from the rest of the chemokine family, which is thought to anchor it to venule endothelium where the amino terminus can interact with its cognate receptor, CCR7. We and others have reported that venule endothelium expressing CCL21 plays a crucial role in attracting naïve immune cells to sites of antigen presentation. In this study we generated a series of monoclonal antibodies to the amino terminus of CCL21 in an attempt to generate an antibody that blocked the interaction of CCL21 with its receptor CCR7. We found one humanized clone that blocked naïve T-cell migration towards CCL21, while memory effector T-cells were less affected. Using this monoclonal antibody, we also demonstrated that CCL21 is expressed in the mucosal venule endothelium of the large majority of inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and also in celiac disease. This expression correlated with active IBD in 5 of 6 cases, whereas none of 6 normal bowel biopsies had CCL21 expression. This study raises the possibility that this monoclonal antibody could be used to diagnose initial or recurrent of IBD. Significantly, this antibody could also be used for therapeutic intervention in IBD by selectively interfering with recruitment of naïve immune effector cells to sites of antigen presentation, without harming overall memory immunity.Maegan L CapitanoAruna JaiswalHal E BroxmeyerYilianys PrideSarah GloverFatemah G AmlashiAustin KirbyGayathri SrinivasanElizabeth A WilliamsonDaniel MaisRobert HromasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0252805 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maegan L Capitano Aruna Jaiswal Hal E Broxmeyer Yilianys Pride Sarah Glover Fatemah G Amlashi Austin Kirby Gayathri Srinivasan Elizabeth A Williamson Daniel Mais Robert Hromas A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
description	Chemokines are small proteins that promote leukocyte migration during development, infection, and inflammation. We and others isolated the unique chemokine CCL21, a potent chemo-attractant for naïve T-cells, naïve B-cells, and immature dendritic cells. CCL21 has a 37 amino acid carboxy terminal extension that is distinct from the rest of the chemokine family, which is thought to anchor it to venule endothelium where the amino terminus can interact with its cognate receptor, CCR7. We and others have reported that venule endothelium expressing CCL21 plays a crucial role in attracting naïve immune cells to sites of antigen presentation. In this study we generated a series of monoclonal antibodies to the amino terminus of CCL21 in an attempt to generate an antibody that blocked the interaction of CCL21 with its receptor CCR7. We found one humanized clone that blocked naïve T-cell migration towards CCL21, while memory effector T-cells were less affected. Using this monoclonal antibody, we also demonstrated that CCL21 is expressed in the mucosal venule endothelium of the large majority of inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and also in celiac disease. This expression correlated with active IBD in 5 of 6 cases, whereas none of 6 normal bowel biopsies had CCL21 expression. This study raises the possibility that this monoclonal antibody could be used to diagnose initial or recurrent of IBD. Significantly, this antibody could also be used for therapeutic intervention in IBD by selectively interfering with recruitment of naïve immune effector cells to sites of antigen presentation, without harming overall memory immunity.
format	article
author	Maegan L Capitano Aruna Jaiswal Hal E Broxmeyer Yilianys Pride Sarah Glover Fatemah G Amlashi Austin Kirby Gayathri Srinivasan Elizabeth A Williamson Daniel Mais Robert Hromas
author_facet	Maegan L Capitano Aruna Jaiswal Hal E Broxmeyer Yilianys Pride Sarah Glover Fatemah G Amlashi Austin Kirby Gayathri Srinivasan Elizabeth A Williamson Daniel Mais Robert Hromas
author_sort	Maegan L Capitano
title	A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
title_short	A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
title_full	A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
title_fullStr	A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
title_full_unstemmed	A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.
title_sort	humanized monoclonal antibody against the endothelial chemokine ccl21 for the diagnosis and treatment of inflammatory bowel disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/1ea93e54ea7d4c8bb8880efa6b63ef0d
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A humanized monoclonal antibody against the endothelial chemokine CCL21 for the diagnosis and treatment of inflammatory bowel disease.

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