High impact information on ITGAD

• The leukocyte integrin gene CD11d is repressed by gut-enriched Kruppel-like factor 4 in myeloid cells [1].
• The myeloid-specific leukocyte integrin CD11d encodes the alphaD subunit for the alphaDbeta2 receptor [1].
• Purified GST-GKLFa protein was shown to bind within the -61 to -44 region that overlaps a binding site for the CD11d transcriptional activators Sp1 and transforming growth factor beta-inducible early gene-1 (TIEG1) [1].
• We propose that up-regulation of CD11d expression following differentiation of myeloid cells is mediated through increased binding of TIEG1 binding to the CD11d promoter [2].
• We have isolated a genomic clone that contains CD11d and showed this gene to be 11,461 bp downstream and oriented in the same direction as the related CD11c gene [3].

Biological context of ITGAD

• The ITGAD gene is highly homologous to the three previously known alpha subunit-encoding genes, that compose the beta 2 integrin family, in deduced amino acid sequence, intron/exon structure and mapping location (chromosome 16p11) [4].
• Together, these results show that myelomonocyte-specific phorbol ester down-regulation of CD11d is mediated through both Sp1 and Sp3 [3].
• Transfection analysis showed that down-regulation of CD11d expression by phorbol ester was myelomonocyte-specific and is mediated by one or more cis-elements within the -173 to +74 region [3].
• Upon differentiation of myeloid cells and subsequent up-regulation of CD11d expression, TIEG1 occupancy increases [2].

Anatomical context of ITGAD

• GKLFa physically associates with the histone deacetylases (HDAC) 1 and 2, and both HDACs are bound to the CD11d promoter in vivo but released after exposure of myeloid cells to phorbol ester suggesting that GKLF/GKLFa recruits HDACs to effect repression [1].
• CONCLUSION: The leukointegrin alpha d/CD18 is expressed constitutively by synovial macrophages and macrophage-like lining cells [5].
• In contrast, overexpression of Sp3 in IM9 and Jurkat cells down-regulated CD11d promoter expression [3].
• This suggests that expression of CD11d is coordinately regulated with expression of LDL receptors and the development of the foam cell [6].
• Expression of CD11d reappears in peripheral blood monocytes differentiating to macrophage foam cells [6].

Physical interactions of ITGAD

• A yeast one-hybrid screen showed that a longer isoform of gut-enriched Kruppel-like factor 4 (GKLF) we term GKLFa interacts with the CD11d promoter [1].

Other interactions of ITGAD

• OBJECTIVE: To define the synovial distribution of the novel leukointegrin alpha d/CD18, and compare this with other members of the beta 2-integrin family of adhesion molecules, and their counter-receptors [5].

Analytical, diagnostic and therapeutic context of ITGAD

• Site-directed mutagenesis of the -100 to -20 region of the CD11d promoter revealed transcription factor binding sites essential for expression of this gene [6].
• The leukointegrin alpha d/beta 2 (alpha d/CD18): specific changes in surface expression in patients on hemodialysis [7].

References