PuSH - Publikationsserver des Helmholtz Zentrums München

Aschenbrenner, D.* ; Ye, Z.* ; Zhou, Y.* ; Hu, W.* ; Brooks, I.* ; Williams, I.* ; Capitani, M.* ; Gartner, L.* ; Kotlarz, D.M. ; Snapper, S.B.* ; Klein, C.* ; Muise, A.M.* ; Marsden, B.D.* ; Huang, Y.* ; Uhlig, H.H.*

Pathogenic interleukin-10 receptor alpha variants in humans - balancing natural selection and clinical implications.

J. Clin. Immunol., DOI: 10.1007/s10875-022-01366-7 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We identify 36 non-synonymous and non-sense variants in the IL10RA gene. Since the majority of these IL10RA variants have not been functionally characterized, we performed a systematic screening of their impact on STAT3 phosphorylation upon IL-10 stimulation. Based on the geographic accumulation of confirmed pathogenic IL10RA variants in East Asia and in Northeast China, the distribution of infectious disorders worldwide, and the functional evidence of IL-10 signaling in the pathogenesis, we identify Schistosoma japonicum infection as plausible selection pressure driving variation in IL10RA. Consistent with this is a partially augmented IL-10 response in peripheral blood mononuclear cells from heterozygous variant carriers. A parasite-driven heterozygote advantage through reduced IL-10 signaling has implications for health care utilization in regions with high allele frequencies and potentially indicates pathogen eradication strategies that target IL-10 signaling.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Il-10 ; Il10ra ; Inflammatory Bowel Disease ; Natural Selection
ISSN (print) / ISBN 0271-9142
e-ISSN 1573-2592
Zeitschrift Journal of Clinical Immunology
Verlag Springer
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)