Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.

<h4>Background</h4>CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays va...

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Autores principales:	Jérôme Rambert, Maria Mamani-Matsuda, Daniel Moynet, Pierre Dubus, Vanessa Desplat, Tina Kauss, Joël Dehais, Thierry Schaeverbeke, Khaled Ezzedine, Denis Malvy, Philippe Vincendeau, M Djavad Mossalayi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce0b1a8da78b4493ab5d2aec3d80b7e2
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spelling	oai:doaj.org-article:ce0b1a8da78b4493ab5d2aec3d80b7e22021-11-25T06:16:44ZMolecular blocking of CD23 supports its role in the pathogenesis of arthritis.1932-620310.1371/journal.pone.0004834https://doaj.org/article/ce0b1a8da78b4493ab5d2aec3d80b7e22009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19279679/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified.<h4>Methodology/principal findings</h4>We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis.<h4>Conclusion</h4>CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23.Jérôme RambertMaria Mamani-MatsudaDaniel MoynetPierre DubusVanessa DesplatTina KaussJoël DehaisThierry SchaeverbekeKhaled EzzedineDenis MalvyPhilippe VincendeauM Djavad MossalayiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4834 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jérôme Rambert Maria Mamani-Matsuda Daniel Moynet Pierre Dubus Vanessa Desplat Tina Kauss Joël Dehais Thierry Schaeverbeke Khaled Ezzedine Denis Malvy Philippe Vincendeau M Djavad Mossalayi Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
description	<h4>Background</h4>CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified.<h4>Methodology/principal findings</h4>We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis.<h4>Conclusion</h4>CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23.
format	article
author	Jérôme Rambert Maria Mamani-Matsuda Daniel Moynet Pierre Dubus Vanessa Desplat Tina Kauss Joël Dehais Thierry Schaeverbeke Khaled Ezzedine Denis Malvy Philippe Vincendeau M Djavad Mossalayi
author_facet	Jérôme Rambert Maria Mamani-Matsuda Daniel Moynet Pierre Dubus Vanessa Desplat Tina Kauss Joël Dehais Thierry Schaeverbeke Khaled Ezzedine Denis Malvy Philippe Vincendeau M Djavad Mossalayi
author_sort	Jérôme Rambert
title	Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
title_short	Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
title_full	Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
title_fullStr	Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
title_full_unstemmed	Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
title_sort	molecular blocking of cd23 supports its role in the pathogenesis of arthritis.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/ce0b1a8da78b4493ab5d2aec3d80b7e2
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Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.

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