| Autor: |
Vasiliki Lagou, Josselyn E. Garcia-Perez, Ide Smets, Lies Van Horebeek, Marijne Vandebergh, Liye Chen, Klara Mallants, Teresa Prezzemolo, Kelly Hilven, Stephanie Humblet-Baron, Matthieu Moisse, Philip Van Damme, Guy Boeckxstaens, Paul Bowness, Bénédicte Dubois, James Dooley, Adrian Liston, An Goris |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 25, Iss 3, Pp 798-810.e6 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2018.09.048 |
| Popis: |
Summary: The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%–20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation. Genetic variation controlling disease-relevant T helper cell subsets includes RICTOR and STON2 associated with Th2 and Th17, respectively, and the interferon-lambda locus controlling regulatory T cell proliferation. Early and memory B cell differentiation stages are associated with variation in LARP1B and SP4. Finally, the latrophilin family member ADGRL2 correlates with baseline pro-inflammatory interleukin-6 levels. Suggestive associations reveal mechanisms of autoimmune disease associations, in particular related to pro-inflammatory cytokine production. Pinpointing these key human immune regulators offers attractive therapeutic perspectives. : Lagou et al. identify genetic factors explaining interindividual variation in composition of the adaptive immune system. Factors pinpoint key human immune regulators controlling B and T cell differentiation and levels of disease-relevant T helper and regulatory cells. These findings shed light on mechanisms of autoimmune disease and offer therapeutic perspectives. Keywords: adaptive immune system, immune phenotype, genetics, association, genome-wide association, autoimmunity, susceptibility |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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