Association of TNFSF8 Polymorphisms With Peripheral Neutrophil Count
MAYO CLINIC PROCEEDINGS
Authors: Arruda-Olson, Adelaide M.; Roger, Veronique L.; Chai, High S.; de Andrade, Mariza; Fridley, Brooke L.; Cunningham, Julie M.; Gabriel, Sherine E.; Bielinski, Suzette J.
Abstract
OBJECTIVE: To investigate the association between 347 single-nucleotide polymorphisms within candidate genes of the tumor necrosis factor, interleukin 1 and interieukin 6 families with neutrophil count. PATIENTS AND METHODS: Four hundred cases with heart failure after myocardial Infarction (MI) were matched by age, sex, and date of incident MI to 694 controls (MI without post-MI heart failure). Both genotypes and neutrophil count at admission for incident MI were available in 314 cases and 515 controls. RESULTS: We found significant associations between the TNFSF8 polymorphisms rs927374 (P=5.1 x 10(-5)) and rs2295800 (P=1.3 x 10(-4)) and neutrophil count; these single-nucleotide polymorphisms are in high linkage dlsequilibrium (r(2)=0.97). Associations persisted after controlling for clinical characteristics and were unchanged after adjusting for case-control status. For rs927374, the neutrophil count of GG homozygotes (7.6 +/- 5.1) was 16% lower than that of CC homozygotes (9.0 +/- 5.2). CONCLUSION: The TNFSF8 poiymorphisms rs927374 and rs2295800 were associated with neutrophil count. This finding suggests that post-MI inflammatory response is genetically modulated. Mayo Clin Proc. 2011;86(11):1075-1081
A novel role for reciprocal CD30-CD30L signaling in the cross-talk between natural killer and dendritic cells
BIOLOGICAL CHEMISTRY
Authors: Simhadri, Vijaya Lakshmi; Hansen, Hinrich P.; Simhadri, Venkateswara R.; Reiners, Katrin S.; Bessler, Martina; Engert, Andreas; von Strandmann, Elke Pogge
Abstract
The interplay between dendritic cells (DCs) and natural killer (NK) cells directs adaptive immune responses. The molecular basis of the cross-talk is largely undefined. Here, we provide evidence for a contribution of CD30 (TNFRSF8) and its ligand CD30L (TNFSF8) expressed on NK cells and DCs, respectively. We demonstrate that CD30-mediated engagement of CD30L induced cytokine secretion from immature DCs via the mitogen-activated protein kinase pathway. Moreover, CD30L engagement promoted differentiation to mature DCs. On the contrary, the engagement of CD30 on NK cells resulted in an NF-kappa B-dependent release of TNF-alpha/IFN-gamma. These data uncover a novel and unexpected role for CD30/CD30L that contributes to proinflammatory immune responses.