Intrinsic renal cell expression of CD40 directs Th1 effectors inducing experimental crescentic glomerulonephritis.
Evidence suggests that human and experimental crescentic GN results from Th1-predominant immunity to glomerular antigens. CD40/ CD154 signaling plays a key role in initiating Th1 responses and may direct Th1 effector responses. The role of CD40 in the development of GN was assessed in murine experimental anti-glomerular basement membrane GN. In this model, C57BL/6 wild-type (WT) mice sensitized to sheep globulin develop crescentic GN resulting from Th1 effector responses when challenged with sheep globulin planted in glomeruli. CD40-/- mice do not develop immunity in response to sheep globulin and thus fail to develop effector responses or significant GN. CD40 is expressed in nephritic glomeruli, suggesting a potential role for intrarenal CD40- CD154 interactions in injurious effector responses. Immune neutralization of the CD40 ligand ( CD154) at the time of challenge significantly reduced accumulation of Th1 effectors and injury. The role of CD40 expression by renal cells was assessed by comparing GN in WT-->CD40-/- chimeras (absent renal but intact bone marrow CD40) and sham chimeric mice (WT-->WT). Both groups developed strong antigen-specific immune responses (antibody and IFN-gamma production). However, WT-->CD40-/- chimeras demonstrated reduced renal monocyte chemotactic protein 1 and IFN-inducible protein 10 mRNA levels and minimal T cell and macrophage influx and were protected from renal injury. Sham chimeric mice developed reduced GFR, with prominent renal expression of monocyte chemotactic protein 1 and IFN-inducible protein 10 mRNA and effector cell accumulation. In conclusion, the expression of CD40 by nonimmune renal cells plays a major role in Th1 effector responses by inducing Th1 chemokine production. Therefore, CD40- CD154 interactions are a potential therapeutic target in GN.[1]References
- Intrinsic renal cell expression of CD40 directs Th1 effectors inducing experimental crescentic glomerulonephritis. Ruth, A.J., Kitching, A.R., Semple, T.J., Tipping, P.G., Holdsworth, S.R. J. Am. Soc. Nephrol. (2003) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
