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排序方式: 共有125条查询结果,搜索用时 15 毫秒
91.
Ghoreschi K Laurence A Yang XP Tato CM McGeachy MJ Konkel JE Ramos HL Wei L Davidson TS Bouladoux N Grainger JR Chen Q Kanno Y Watford WT Sun HW Eberl G Shevach EM Belkaid Y Cua DJ Chen W O'Shea JJ 《Nature》2010,467(7318):967-971
CD4(+) T-helper cells that selectively produce interleukin (IL)-17 (T(H)17), are critical for host defence and autoimmunity. Although crucial for T(H)17 cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been proposed to be the factors responsible for initiating specification. Here we show that T(H)17 differentiation can occur in the absence of TGF-β signalling. Neither IL-6 nor IL-23 alone efficiently generated T(H)17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naive precursors, independently of TGF-β. Epigenetic modification of the Il17a, Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed RORγt (encoded by Rorc) and T-bet. T-bet(+)RORγt(+) T(H)17 cells are generated in vivo during experimental allergic encephalomyelitis, and adoptively transferred T(H)17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data indicate an alternative mode for T(H)17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore may have therapeutic implications. 相似文献
92.
M. O'Brien T. McCarthy D. Jenkins P. Paul J. Dausset E.D. Carosella P. Moreau 《Cellular and molecular life sciences : CMLS》2001,58(12-13):1943-1949
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95.
Easton DF Pooley KA Dunning AM Pharoah PD Thompson D Ballinger DG Struewing JP Morrison J Field H Luben R Wareham N Ahmed S Healey CS Bowman R;SEARCH collaborators Meyer KB Haiman CA Kolonel LK Henderson BE Le Marchand L Brennan P Sangrajrang S Gaborieau V Odefrey F Shen CY Wu PE Wang HC Eccles D Evans DG Peto J Fletcher O Johnson N Seal S Stratton MR Rahman N Chenevix-Trench G Bojesen SE Nordestgaard BG Axelsson CK Garcia-Closas M Brinton L Chanock S Lissowska J Peplonska B Nevanlinna H 《Nature》2007,447(7148):1087-1093
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. 相似文献
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97.
A common genetic risk factor for colorectal and prostate cancer 总被引:14,自引:0,他引:14
Haiman CA Le Marchand L Yamamato J Stram DO Sheng X Kolonel LN Wu AH Reich D Henderson BE 《Nature genetics》2007,39(8):954-956
Variants on chromosome 8q24 contribute risk for prostate cancer; here, we tested whether they also modulate risk for colorectal cancer. We studied 1,807 affected individuals and 5,511 controls and found that one variant, rs6983267, is also significantly associated with colorectal cancer (odds ratio = 1.22; P = 4.4 x 10(-6)) and that the apportionment of risk among the variants differs significantly between the two cancers. Comprehensive testing in the region uncovered variants capturing significant additional risk. Our results show that variants at 8q24 have different effects on cancer development that depend on the tissue type. 相似文献
98.
Tauzin S Debure L Moreau JF Legembre P 《Cellular and molecular life sciences : CMLS》2012,69(8):1261-1277
Apoptosis has emerged as a fundamental process important in tissue homeostasis, immune response, and during development. CD95
(also known as Fas), a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been initially cloned as a death
receptor. Its cognate ligand, CD95L, is mainly found at the plasma membrane of activated T-lymphocytes and natural killer
cells where it contributes to the elimination of transformed and infected cells. According to its implication in the immune
homeostasis and immune surveillance, and since several malignant cells of various histological origins exhibit loss-of-function
mutations, which cause resistance towards the CD95-mediated apoptotic signal, CD95 has been classified as a tumor suppressor
gene. Nevertheless, this assumption has been recently challenged, as in certain pathophysiological contexts, CD95 engagement
transmits non-apoptotic signals that promote inflammation, carcinogenesis or liver/peripheral nerve regeneration. The focus
of this review is to discuss these apparent contradictions of the known function(s) of CD95. 相似文献
99.
Van Houdt JK Nowakowska BA Sousa SB van Schaik BD Seuntjens E Avonce N Sifrim A Abdul-Rahman OA van den Boogaard MJ Bottani A Castori M Cormier-Daire V Deardorff MA Filges I Fryer A Fryns JP Gana S Garavelli L Gillessen-Kaesbach G Hall BD Horn D Huylebroeck D Klapecki J Krajewska-Walasek M Kuechler A Lines MA Maas S Macdermot KD McKee S Magee A de Man SA Moreau Y Morice-Picard F Obersztyn E Pilch J Rosser E Shannon N Stolte-Dijkstra I Van Dijck P Vilain C Vogels A Wakeling E Wieczorek D 《Nature genetics》2012,44(4):445-9, S1
100.
Donadi EA Castelli EC Arnaiz-Villena A Roger M Rey D Moreau P 《Cellular and molecular life sciences : CMLS》2011,68(3):369-395
The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of
the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system.
Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and
3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism
observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas,
in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory
properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized
approach for the future use of HLA-G for therapeutic purposes. 相似文献