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Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4+ T Helper Cell Responses.
Journal of Immunology Research ( IF 4.1 ) Pub Date : 2020-08-03 , DOI: 10.1155/2020/1421795
Irem Ozel 1 , Ilgin Akkaya 1 , Ece Oylumlu 1 , Goksu Uzel 1 , Ceren Ciraci 1
Affiliation  

NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive immune responses in a caspase-1-independent manner. We examined the regulation and mechanism of adenosine responsiveness via NLRP11 in human Daudi Burkitt’s B lymphoma cells and their effects on human peripheral CD4+ T lymphocytes from healthy individuals. NLRP11 was significantly upregulated after induction with adenosine at both the mRNA and protein levels, which led to the interaction of endogenous NLRP11 with the ASC adaptor protein; however, this interaction did not result in the activation of the caspase-1 enzyme. Furthermore, cocultures of NLRP11-expressing Burkitt’s lymphoma cells and naïve human peripheral CD4+ T lymphocytes had reduced IFN-γ and IL-17A production, whereas IL-13 and IL-10 cytokines did not change. Interestingly, IFN-γ and IL-17A were recovered after transfection of Burkitt’s lymphoma cells with siRNAs targeting NLRP11. Concomitant with NLRP11 upregulation, we also exhibited that adenosine A2B receptor signaling induced two phosphorylated downstream effectors, pErk1/2 and pAkt (Ser473), but not pAkt (Thr308). Taken together, our data indicate that adenosine is a negative regulator of Th1 and Th17 responses via NLRP11 in an inflammasome-independent manner.

中文翻译:

B淋巴母细胞中腺苷诱导的NLRP11抑制人CD4 + T辅助细胞反应。

NLRP11是包含PYD域的,核苷酸结合的寡聚域(NOD-)样受体(NLR)家族的成员。迄今为止尚未真正了解NLRP11的真正刺激作用,因此当前的研究建立在通过腺苷刺激进行NLRP11诱导的基础上,并且该激活可以以caspase-1独立的方式塑造适应性免疫应答。我们研究了人Daudi Burkitt B淋巴瘤细胞中通过NLRP11调节腺苷反应的机制和机制,以及它们对人外周CD4 +的影响来自健康个体的T淋巴细胞。腺苷诱导后,NLRP11在mRNA和蛋白水平上均显着上调,这导致内源性NLRP11与ASC衔接蛋白相互作用。但是,这种相互作用不会导致caspase-1酶的激活。此外,表达NLRP11的伯基特氏淋巴瘤细胞和未经处理的人外周血CD4 + T淋巴细胞的共培养降低了IFN- γ和IL-17A的产生,而IL-13和IL-10细胞因子未改变。有趣的是,用靶向NLRP11的siRNA转染Burkitt淋巴瘤细胞后,IFN- γ和IL-17A得以回收。伴随着NLRP11上调,我们还展示了腺苷A 2B受体信号传导诱导了两个磷酸化的下游效应子,pErk1 / 2和pAkt(Ser473),但不诱导pAkt(Thr308)。两者合计,我们的数据表明腺苷是独立于炎性体的方式,通过NLRP11对Th1和Th17反应的负调节剂。
更新日期:2020-08-03
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