Acute FPIES reactions are associated with an IL-17 inflammatory signature.
Acute FPIES reactions are associated with an IL-17 inflammatory signature.
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急性FPIES反应与IL-17炎症信号有关。
DOI：
10.1016/j.jaci.2021.04.012
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Nowak-Wegrzyn A
中科院分区：
文献类型：
--
作者：
Berin MC;Lozano-Ojalvo D;Agashe C;Baker MG;Bird JA;Nowak-Wegrzyn A
食物蛋白诱导的小肠结肠炎综合征（FPIES）是一种非IgE介导的食物过敏，其特征是摄入致病食物后数小时内大量呕吐。我们以前曾报道，FPIES与系统性先天免疫激活的情况下，可检测的抗原特异性抗体或T细胞反应。免疫系统识别特定食物的机制尚不清楚。通过外周血蛋白质组学和流式细胞术分析，确定FPIES反应的免疫机制。有FPIES病史的儿童接受了有监督的口服食物挑战。在基线时、症状发作时和症状后4小时采集血样。我们分析了23名儿童（11名反应者，12名发育不良）的样本。184个蛋白质标记通过邻位连接分析进行分析，并通过多重免疫分析进行验证。通过质谱细胞术和光谱细胞术进行细胞亚群活化的分析。症状FPIES激发与细胞因子和趋化因子显著升高相关，包括IL-17家族标志物（IL-17 A、IL-22、IL-17 C、CCL 20）、T细胞活化（IL-2）和先天性炎症标志物（IL-8、抑瘤素M、LIF、TNFα、IL-10、IL-6）。粘膜损伤标志物REG 1A也显着增加。这些生物标志物在无症状激发或IgE介导的过敏中未增加。在有症状的个体中，激发后骨髓和T细胞中磷酸化STAT 3显著升高。流式细胞术显示非常规T细胞群优先活化，包括γδ T细胞和CD 3 + CD 4-CD 8-CD 161+细胞，然而PBMC中IL-17的潜在来源主要是CD 4 + Th 17细胞。这些结果证明了FPIES中独特的IL-17特征和先天淋巴细胞的激活。症状FPIES激发导致与先天性IL-17应答和粘膜屏障损伤相关的标志物的全身释放。
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T cell response. The mechanism of specific food recognition by the immune system remains unclear. To identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood. Children with a history of FPIES underwent a supervised oral food challenge. Blood samples were taken at baseline, upon symptom onset, and 4 h post-symptoms. We analyzed samples from 23 children (11 reactors, 12 outgrown). 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry. Symptomatic FPIES challenges were associated with significant elevation of cytokines and chemokines including IL-17 family markers (IL-17A, IL-22, IL-17C, CCL20), T cell activation (IL-2), and innate inflammatory markers (IL-8, Oncostatin M, LIF, TNFα, IL-10, IL-6). The mucosal damage marker REG1A was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. Phospho-STAT3 was significantly elevated in myeloid and T cells post-challenge in individuals with symptoms. Mass cytometry indicated preferential activation of non-conventional T cell populations, including γδ T cells and CD3+CD4-CD8-CD161+ cells, however the potential sources of IL-17 in PBMCs were primarily CD4+ Th17 cells. These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES. Symptomatic FPIES challenges resulted in a systemic release of markers associated with an innate IL-17 response and mucosal barrier damage.
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DOI：
10.1016/j.jaci.2018.01.044
发表时间：
2018-07
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Berin MC;Grishin A;Masilamani M;Leung DYM;Sicherer SH;Jones SM;Burks AW;Henning AK;Dawson P;Grabowska J;Agashe C;Davidson WF;Wood RA;Sampson HA
通讯作者：
Sampson HA
影响因子：
14.2
作者：
Chiang, David;Chen, Xintong;Berin, M. Cecilia
通讯作者：
Berin, M. Cecilia
影响因子：
8
作者：
Bartolome-Casado, Raquel;Landsverk, Ole J. B.;Jahnsen, Frode L.
通讯作者：
Jahnsen, Frode L.
影响因子：
14.2
作者：
Nowak-Wegrzyn, Anna;Chehade, Mirna;Greenhawt, Matthew
通讯作者：
Greenhawt, Matthew
影响因子：
4.4
作者：
Adel-Patient K;Lezmi G;Castelli FA;Blanc S;Bernard H;Soulaines P;Dumond P;Ah-Leung S;Lageix F;de Boissieu D;Cortes-Perez N;Hazebrouck S;Fenaille F;Junot C;Dupont C
通讯作者：
Dupont C