FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307135092> ?p ?o ?g. }

• W4307135092 abstract "Abstract Background Ligation of CD28 with ligands such as CD80 or CD86 provides a critical second signal alongside antigen presentation by class II major histocompatibility complex expressed on antigen-presenting cells through the T cell antigen receptor for naïve T cell activation. A number of studies suggested that CD28 plays an important role in the pathogenesis of various human diseases. Recent genome-wide association studies (GWASs) identified CD28 as a susceptibility locus for lymphocyte and eosinophil counts, multiple sclerosis, ulcerative colitis, celiac disease, rheumatoid arthritis, asthma, and primary biliary cholangitis. However, the primary functional variant and molecular mechanisms of disease susceptibility in this locus remain to be elucidated. This study aimed to identify the primary functional variant from thousands of genetic variants in the CD28 locus and elucidate its functional effect on the CD28 molecule. Results Among the genetic variants exhibiting stronger linkage disequilibrium (LD) with all GWAS-lead variants in the CD28 locus, rs2013278, located in the Rbfox binding motif related to splicing regulation, was identified as a primary functional variant related to multiple immunological traits. Relative endogenous expression levels of CD28 splicing isoforms (CD28i and CD28Δex2) compared with full-length CD28 in allele knock-in cell lines generated using CRISPR/Cas9 were directly regulated by rs2013278 (P < 0.05). Although full-length CD28 protein expressed on Jurkat T cells showed higher binding affinity for CD80/CD86, both CD28i and CD28Δex2 encoded loss-of-function isoforms. Conclusion The present study demonstrated for the first time that CD28 has a shared disease-related primary functional variant (i.e., rs2013278) that regulates the CD28 alternative splicing that generates loss-of-function isoforms. They reduce disease risk by inducing anergy of effector T cells that over-react to autoantigens and allergens." @default.
• W4307135092 created "2022-10-28" @default.
• W4307135092 creator A5001942683 @default.
• W4307135092 creator A5007318261 @default.
• W4307135092 creator A5010200602 @default.
• W4307135092 creator A5016476726 @default.
• W4307135092 creator A5018467555 @default.
• W4307135092 creator A5023897064 @default.
• W4307135092 creator A5025220924 @default.
• W4307135092 creator A5029150547 @default.
• W4307135092 creator A5030939408 @default.
• W4307135092 creator A5040367383 @default.
• W4307135092 creator A5057044610 @default.
• W4307135092 creator A5060357125 @default.
• W4307135092 creator A5068093284 @default.
• W4307135092 date "2022-10-21" @default.
• W4307135092 modified "2023-10-10" @default.
• W4307135092 title "rs2013278 in the multiple immunological-trait susceptibility locus CD28 regulates the production of non-functional splicing isoforms" @default.
• W4307135092 cites W1014257459 @default.
• W4307135092 cites W1489480103 @default.
• W4307135092 cites W1498093713 @default.
• W4307135092 cites W1519521580 @default.
• W4307135092 cites W1541965214 @default.
• W4307135092 cites W1570594698 @default.
• W4307135092 cites W1967067685 @default.
• W4307135092 cites W1975705143 @default.
• W4307135092 cites W1979723012 @default.
• W4307135092 cites W1985158145 @default.
• W4307135092 cites W1985905844 @default.
• W4307135092 cites W1989270381 @default.
• W4307135092 cites W1989590412 @default.
• W4307135092 cites W1993219448 @default.
• W4307135092 cites W1994154030 @default.
• W4307135092 cites W2009059990 @default.
• W4307135092 cites W2018838463 @default.
• W4307135092 cites W2032466777 @default.
• W4307135092 cites W2040375465 @default.
• W4307135092 cites W2044480628 @default.
• W4307135092 cites W2048073154 @default.
• W4307135092 cites W2055420557 @default.
• W4307135092 cites W2064927494 @default.
• W4307135092 cites W2068558726 @default.
• W4307135092 cites W2075516845 @default.
• W4307135092 cites W2076118745 @default.
• W4307135092 cites W2076194704 @default.
• W4307135092 cites W2081255498 @default.
• W4307135092 cites W2081936911 @default.
• W4307135092 cites W2083311645 @default.
• W4307135092 cites W2086776723 @default.
• W4307135092 cites W2090481553 @default.
• W4307135092 cites W2104873001 @default.
• W4307135092 cites W2105170173 @default.
• W4307135092 cites W2106876831 @default.
• W4307135092 cites W2112709855 @default.
• W4307135092 cites W2119931665 @default.
• W4307135092 cites W2121498145 @default.
• W4307135092 cites W2128016314 @default.
• W4307135092 cites W2132576596 @default.
• W4307135092 cites W2135403800 @default.
• W4307135092 cites W2141989396 @default.
• W4307135092 cites W2143592689 @default.
• W4307135092 cites W2146195401 @default.
• W4307135092 cites W2153384396 @default.
• W4307135092 cites W2162856391 @default.
• W4307135092 cites W2166320441 @default.
• W4307135092 cites W2167697292 @default.
• W4307135092 cites W2214789582 @default.
• W4307135092 cites W2339326063 @default.
• W4307135092 cites W2395845086 @default.
• W4307135092 cites W2508268289 @default.
• W4307135092 cites W2508425869 @default.
• W4307135092 cites W2613629789 @default.
• W4307135092 cites W2620311549 @default.
• W4307135092 cites W2735553444 @default.
• W4307135092 cites W2777667999 @default.
• W4307135092 cites W2801254160 @default.
• W4307135092 cites W2904108970 @default.
• W4307135092 cites W2910846136 @default.
• W4307135092 cites W2911999331 @default.
• W4307135092 cites W2951091314 @default.
• W4307135092 cites W3081528139 @default.
• W4307135092 cites W3082575318 @default.
• W4307135092 cites W3133135588 @default.
• W4307135092 cites W3147403109 @default.
• W4307135092 cites W3150477919 @default.
• W4307135092 cites W3165249197 @default.
• W4307135092 cites W3202209876 @default.
• W4307135092 cites W4200549370 @default.
• W4307135092 cites W4292540530 @default.
• W4307135092 doi "https://doi.org/10.1186/s40246-022-00419-7" @default.
• W4307135092 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36271469" @default.
• W4307135092 hasPublicationYear "2022" @default.
• W4307135092 type Work @default.
• W4307135092 citedByCount "1" @default.
• W4307135092 countsByYear W43071350922023 @default.
• W4307135092 crossrefType "journal-article" @default.
• W4307135092 hasAuthorship W4307135092A5001942683 @default.
• W4307135092 hasAuthorship W4307135092A5007318261 @default.
• W4307135092 hasAuthorship W4307135092A5010200602 @default.
• W4307135092 hasAuthorship W4307135092A5016476726 @default.

• next