Sökning: id:"swepub:oai:DiVA.org:liu-154713" >
The Act1 D10N misse...
The Act1 D10N missense variant impairs CD40 signaling in human B-cells
-
- Yu, Ning (författare)
- Univ Michigan, MI 48109 USA; Shanghai Skin Dis Hosp, Peoples R China
-
- Lambert, Sylviane (författare)
- Univ Michigan, MI 48109 USA
-
- Bornstein, Joshua (författare)
- Univ Michigan, MI 48109 USA
-
visa fler...
-
- Nair, Rajan P. (författare)
- Univ Michigan, MI 48109 USA
-
- Enerbäck, Charlotta (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland,Univ Michigan, MI 48109 USA
-
- Elder, James T. (författare)
- Univ Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hlth Syst, MI 48105 USA
-
visa färre...
-
(creator_code:org_t)
- 2018-01-05
- 2019
- Engelska.
-
Ingår i: Genes and Immunity. - : NATURE PUBLISHING GROUP. - 1466-4879 .- 1476-5470. ; 20:1, s. 23-31
- Relaterad länk:
-
https://europepmc.or...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The TRAF3IP2 gene resides within one of at least 63 psoriasis susceptibility loci and encodes Act1, an adapter protein involved in IL-17 receptor and CD40 signaling pathways. TRAF3IP2 is distinctive (among amp;lt; 10% of candidate susceptibility genes) in that a strongly disease-associated variant encodes a missense SNP predicted to be functionally relevant (SNP rs33980500 C/T encoding Act1 pD10N). As assessed by flow cytometry, Act1 protein was expressed at the highest levels in monocytes, with lower levels in T-cells and B-cells. However, monocytes, T-cells and B-cells failed to respond to IL-17A stimulation of PBMC, as measured by flow cytometric determination of NF-kappa B phospho-p65. As an alternative stimulus, we treated PBMCs with trimerized recombinant human CD40L and assessed p65, p38 and Erk phosphorylation in CD19(+) B-cells as a function of D10N genotype. The increase of phosphorylated p65, p38, and Erk was well-correlated across individuals, and CD40L-induced phosphorylation of p65, p38, and Erk was significantly attenuated in B-cells from Act1 D10N homozygotes, compared to heterozygotes and nullizygotes. Our results indicate that the Act1 D10N variant is a relevant genetic determinant of CD40L responsiveness in human B-cells, with the risk allele being associated with lower B-cell responses in an acute signaling context.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas