title: Molecular blocking of CD23 supports its role in the pathogenesis of arthritis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Groupe Thérapeutiques d'inflammation et d'infection, Laboratoire d'Immunologie et de Parasitologie, UFR Sciences Pharmaceutiques, Université Bordeaux 2, Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rambert
authors.forename: Maria
authors.initials: M
authors.lastname: Mamani-Matsuda
authors.forename: Daniel
authors.initials: D
authors.lastname: Moynet
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.forename: Vanessa
authors.initials: V
authors.lastname: Desplat
authors.forename: Tina
authors.initials: T
authors.lastname: Kauss
authors.forename: Joël
authors.initials: J
authors.lastname: Dehais
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.forename: Denis
authors.initials: D
authors.lastname: Malvy
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.forename: M Djavad
authors.initials: MD
authors.lastname: Mossalayi
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D006801:Humans; D017737:Macrophages, Peritoneal / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D017455:Receptors, IgE