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10.1556/1886.2017.00007

http://scihub22266oqcxt.onion/10.1556/1886.2017.00007
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C5495083!5495083!28690878
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suck abstract from ncbi


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pmid28690878      Eur+J+Microbiol+Immunol+(Bp) 2017 ; 7 (2): 112-26
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  • The Guanine-Nucleotide Exchange Factor Caldag Gefi Fine-Tunes Functional Properties of Regulatory T Cells #MMPMID28690878
  • Niemz J; Kliche S; Pils MC; Morrison E; Manns A; Freund C; Crittenden JR; Graybiel AM; Galla M; Jänsch L; Huehn J
  • Eur J Microbiol Immunol (Bp) 2017[Jun]; 7 (2): 112-26 PMID28690878show ga
  • Using quantitative phosphopeptide sequencing of unstimulated versus stimulated primary murine Foxp3+ regulatory and Foxp3? conventional T cells (Tregs and Tconv, respectively), we detected a novel and differentially regulated tyrosine phosphorylation site within the C1 domain of the guanine-nucleotide exchange factor CalDAG GEFI. We hypothesized that the Treg-specific and activation-dependent reduced phosphorylation at Y523 allows binding of CalDAG GEFI to diacylglycerol, thereby impacting the formation of a Treg-specific immunological synapse. However, diacylglycerol binding assays of phosphomutant C1 domains of CalDAG GEFI could not confirm this hypothesis. Moreover, CalDAG GEFI?/? mice displayed normal Treg numbers in thymus and secondary lymphoid organs, and CalDAG GEFI?/? Tregs showed unaltered in vitro suppressive capacity when compared to CalDAG GEFI+/+ Tregs. Interestingly, when tested in vivo, CalDAG GEFI?/? Tregs displayed a slightly reduced suppressive ability in the transfer colitis model when compared to CalDAG GEFI+/+ Tregs. Additionally, CRISPR-Cas9-generated CalDAG GEFI?/? Jurkat T cell clones showed reduced adhesion to ICAM-1 and fibronectin when compared to CalDAG GEFI-competent Jurkat T cells. Therefore, we speculate that deficiency in CalDAG GEFI impairs adherence of Tregs to antigen-presenting cells, thereby impeding formation of a fully functional immunological synapse, which finally results in a reduced suppressive potential.
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