Cord Blood CD8(+) T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner.
Cord Blood CD8(+) T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner.
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脐带血 CD8( ) T 细胞具有以脂肪酸代谢和 Caspase 激活依赖性方式表达 IL-4 的天然倾向
DOI：
10.3389/fimmu.2018.00879
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发表时间：
2018
影响因子：
7.3
通讯作者：
Harrison LC
中科院分区：
文献类型：
--
作者：
Zhang Y;Maksimovic J;Huang B;De Souza DP;Naselli G;Chen H;Zhang L;Weng K;Liang H;Xu Y;Wentworth JM;Huntington ND;Oshlack A;Gong S;Kallies A;Vuillermin P;Yang M;Harrison LC
T细胞如何在新生儿中分化可能会关键地决定婴儿应对感染、对疫苗作出反应和避免过敏的能力。先前，我们发现naïve脐带血CD4+ T细胞在TGF-β和单核细胞源性炎症细胞因子的激活下向表达il -4的表型分化，后者在发生食物过敏的婴儿中分泌更多。在这里，我们发现在缺乏IL-2或IL-12的情况下，naïve脐带血CD8+ T细胞在单独激活或TGF-β和/或炎症细胞因子存在时具有自然倾向，可分化为产生il -4的非经典TC2细胞。机制上，非经典TC2的发展与IL-2受体α (CD25)和糖酵解的表达降低、脂肪酸代谢增加和caspase依赖性细胞死亡有关。因此，短链脂肪酸丙酸钠（NaPo）增强了IL-4的表达，但外源IL-2或泛caspase抑制了IL-4的表达。在内镜和组织学证实的非炎症性肠病和非传染性儿童特发性结肠炎患儿中，TGF-β、NaPo和IL-1β或TNF-α的存在促进了TC2的体外分化。在体内，结肠炎患儿结肠黏膜CD8+ T细胞中IL-4的表达明显高于对照组。此外，活化的caspase-3和IL-4在结肠炎患儿结肠粘膜CD8+ T细胞中共表达。因此，在结肠炎症和有限的IL-2信号的背景下，CD8+ T细胞分化为非经典的TC2，这可能有助于儿童炎症/过敏性疾病的病理。
How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children.
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影响因子：
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作者：
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通讯作者：
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