Document Detail

CD40 ligation of human keratinocytes inhibits their proliferation and induces their differentiation.
MedLine Citation:
PMID:  8977185     Owner:  NLM     Status:  MEDLINE    
While CD40-CD40 ligand interactions are known to regulate B cell proliferation and differentiation, much less is known about the role this receptor plays on other cell types, especially those of nonhemopoietic origin. We report here that CD40 is expressed in normal human epidermis in situ, especially on the basal cell layer, and that it is maintained on cultured epidermal basal cells. Immunoprecipitation and SDS-PAGE analysis confirms that CD40 expressed by epidermal basal cells is immunologically related to the B cell CD40. IFN-gamma up-regulates CD40 expression on cultured keratinocytes, whereas other proinflammatory cytokines, such as IL-1 or TNF-alpha, have little effects. Using CD40-ligand-transfected L cells (CD40Lc), we demonstrated that CD40 triggering results in an enhanced secretion of both IL-8 and TNF-alpha by cultured epidermal basal cells, suggesting that CD40-CD40L interactions may play a role in amplifying the cutaneous inflammatory reactions. More importantly, we found that keratinocyte proliferation was significantly inhibited when the cells were grown on CD40Lc, as compared with CD32-transfected, or nontransfected, L cells. This inhibitory effect can be reversed substantially by pretreatment of keratinocytes with anti-CD40 mAb. In addition, inhibition of proliferation could be obtained by adding a soluble form of CD40 ligand to the keratinocyte cultures. Interestingly, inhibition of keratinocyte proliferation on CD40Lc correlates with differentiation of the cells, as assessed by morphologic analysis and increased profilaggrin content. Collectively, these results demonstrate that CD40 is expressed and functional on human epidermal basal cells and that, on these cells, CD40 ligation may be a signal for limitation of cell growth and induction of differentiation.
J Péguet-Navarro; C Dalbiez-Gauthier; C Moulon; O Berthier; A Réano; M Gaucherand; J Banchereau; F Rousset; D Schmitt
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  158     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-01-30     Completed Date:  1997-01-30     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  144-52     Citation Subset:  AIM; IM    
INSERM Unit 346, Edouard Herriot Hospital, Lyon, France.
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MeSH Terms
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD40 / biosynthesis,  immunology,  metabolism*,  pharmacology*
CD40 Ligand
Cell Adhesion / drug effects
Cell Differentiation / drug effects
Cell Division / drug effects
Cells, Cultured
Fluorescent Antibody Technique, Indirect
Keratinocytes / drug effects*,  metabolism*
L Cells (Cell Line)
Membrane Glycoproteins / metabolism,  pharmacology
Precipitin Tests
Protein Binding / physiology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD40; 0/Ligands; 0/Membrane Glycoproteins; 147205-72-9/CD40 Ligand

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