Zhang Yuxia, Collier Fiona, Naselli Gaetano, Saffery Richard, Tang Mimi L K, Allen Katrina J, Ponsonby Anne-Louise, Harrison Leonard C, Vuillermin Peter
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. The University of Melbourne, Parkville, Victoria 3010, Australia. Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China.
Barwon Health, Geelong, Victoria 3220, Australia. Deakin University, Geelong, Victoria 3216, Australia.
Sci Transl Med. 2016 Jan 13;8(321):321ra8. doi: 10.1126/scitranslmed.aad4322.
Food allergy is a major health burden in early childhood. Infants who develop food allergy display a proinflammatory immune profile in cord blood, but how this is related to interleukin-4 (IL-4)/T helper 2 (T(H)2)-type immunity characteristic of allergy is unknown. In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4(+) T cell ratio and a lower proportion of natural regulatory T cell (nT(reg)) in relation to duration of labor. CD14(+) monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-β, these inflammatory cytokines suppressed IL-2 expression by CD4(+) T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nT(reg) and diverted the differentiation of both nT(reg) and naïve CD4(+) T cells toward an IL-4-expressing nonclassical TH2 phenotype. These findings provide a mechanistic explanation for susceptibility to food allergy in infants and suggest anti-inflammatory approaches to its prevention.
食物过敏是幼儿期的一项重大健康负担。发生食物过敏的婴儿在脐带血中表现出促炎免疫特征，但这与过敏特有的白细胞介素-4（IL-4）/辅助性T细胞2（TH2）型免疫之间的关系尚不清楚。在一个源自普通人群的出生队列中，我们发现，在发生食物过敏的婴儿中，脐带血单核细胞与CD4+ T细胞的比例较高，且自然调节性T细胞（nTreg）的比例相对于产程较短。食物过敏婴儿的CD14+单核细胞在接触脂多糖后分泌更高量的炎性细胞因子（IL-1β、IL-6和肿瘤坏死因子-α）。在黏膜细胞因子转化生长因子-β存在的情况下，这些炎性细胞因子抑制CD4+ T细胞的IL-2表达。在缺乏IL-2的情况下，炎性细胞因子减少了活化的nTreg数量，并使nTreg和初始CD4+ T细胞的分化转向表达IL-4的非经典TH2表型。这些发现为婴儿食物过敏易感性提供了一种机制解释，并提示了预防食物过敏的抗炎方法。
