Journal of Inflammation (Oct 2011)

The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

  • Hütter Gero,
  • Neumann Martin,
  • Nowak Daniel,
  • Klein Stefan,
  • Klüter Harald,
  • Hofmann Wolf-K

DOI
https://doi.org/10.1186/1476-9255-8-29
Journal volume & issue
Vol. 8, no. 1
p. 29

Abstract

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Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5) is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32) located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD) and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

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