Adipose-derived stromal cell immunosuppression of T cells is enhanced under "physiological" hypoxia
TISSUE & CELL
Authors: Gornostaeva, A. N.; Bobyleva, P. I.; Andreeva, E. R.; Yakubets, D. A.; Buravkova, L. B.
Abstract
Multipotent mesenchymal stromal cells (MSCs) are characterized by immunomodulatory properties along with the high proliferative and paracrine activity, as well as multilineage potency. The effects of MSCs on the T cell adaptive immunity are of a special interest. Low O-2 level (1-7 %) is known to be typical for the putative site of the MSC - T cell interactions. A comparative evaluation of the effects of adipose tissue derived MSC (ASCs) on the mitogen-stimulated T cells at the ambient (20 %) and tissue-related (5 %) O-2 levels demonstrated reduced T cell activation by the HLA-DR expression, decreased pro-inflammatory and increased anti-inflammatory cytokine production in co-culture, inhibited T cell proliferation, with the effects increased at hypoxia. T cell interactions with ASCs resulted in the up-regulation of PDCD1, Foxp3, and TGF beta 1 known to play an important role in the immune response suppression, and in the down-regulation of genes involved in the inflammatory reaction (IL2, IFNG). These changes were significantly increased under hypoxia. M the same time, neither ASCs nor the reduced O-2 level had negative effects on the viability of T cells.
Polymorphisms in inflammation-related genes and the risk of primary varicose veins in ethnic Russians
IMMUNOLOGIC RESEARCH
Authors: Shadrina, Alexandra; Voronina, Elena; Smetanina, Mariya; Tsepilov, Yakov; Sevost'ianova, Kseniya; Shevela, Andrey; Seliverstov, Evgenii; Zakharova, Elena; Ilyukhin, Evgeny; Kirienko, Alexander; Zolotukhin, Igor; Filipenko, Maxim
Abstract
Inflammation was shown to be activated in varicose veins, although its role in the development of vein wall transformation remains inconclusive. We aimed to investigate the influence of 13 inflammation-related single nucleotide polymorphisms (SNPs) TNF rs1800629 and rs3093661, IL1A rs1800587, IL1RN rs4251961, IL6 rs1800795 and rs1800796, IFNG rs2430561, IL10 rs1800896, TGFB1 rs1800469, HIF1A rs11549465, NFKB1 rs28362491, and rs4648068 on the risk of primary varicose veins (PVVs) in ethnic Russians. We genotyped 709 patients with PVVs and 278 individuals without a history of chronic venous disease and performed a single SNP and a haplotype analysis. Several associations with P < 0.05 were revealed in our study. Variant allele HIF1A rs11549465 T, TNF rs3093661 A, and NFKB1 rs28362491 ATTG deletion showed the reverse association with PVV risk, and allele IL6 rs1800795 C was associated with the increased risk of the studied pathology. Haplotype analysis revealed associations of TNF haplotypes rs3093661 A-rs1800629 G and IL6 rs1800795 C-rs1800796 G with the decreased and the increased risk of PVVs, correspondingly. However, all the observed associations failed to reach statistical significance after the correction for multiple testing, which was set at a level of 10(-3) due to many tests performed. Our study therefore provides evidence that investigated polymorphisms do not play a major role in susceptibility to PVVs.