期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 148, 期 1, 页码 182-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.11.047
关键词
Peanut allergy; peanut; dendritic cells; monocytes; RALDH2; TLR2; retinoic acid; T(H)2; IL-5; integrin alpha(4)beta(7)
资金
- National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases [K08 AI067722, K08 AI067722-03S1, U19 AI095261]
- U.S. Department of Agriculture, Agricultural Research Service [USDA-ARS-6054-43440-046-00D]
- Food Allergy Science Initiative
- Massachusetts General Hospital
Peanut protein induces RALDH2 in human APCs through signaling receptors TLR1/TLR2, leading to RA production and promoting IL-5 secretion and gut-homing integrin expression in T(H)2 cells.
Background: Peanut is a potent inducer of proallergenic T(H)2 responses in susceptible individuals. Antigen-presenting cells (APCs) including dendritic cells and monocytes instruct naive T cells to differentiate into various effector cells, determining immune responses such as allergy and tolerance. Objective: We sought to detect peanut protein (PN)-induced changes in gene expression in human myeloid dendritic cells (mDCs) and monocytes, identify signaling receptors that mediate these changes, and assess how PN-induced genes in mDCs impact their ability to promote T-cell differentiation. Methods: mDCs, monocytes, and naive CD4(+) T cells were isolated from blood bank donors and peanut-allergic patients. APCs were incubated with PN and other stimulants, and gene expression was measured using microarray and RT quantitative PCR. To assess T-cell differentiation, mDCs were cocultured with naive T-H cells. Results: PN induced a unique gene expression profile in mDCs, including the gene that encodes retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in the retinoic acid (RA)-producing pathway. Stimulation of mDCs with PN also induced a 7-fold increase in the enzymatic activity of RALDH2. Blocking antibodies against Toll-like receptor (TLR)1/TLR2, as well as small interfering RNA targeting TLR1/TLR2, reduced the expression of RALDH2 in PN-stimulated APCs by 70%. Naive TH cells cocultured with PN-stimulated mDCs showed an RA-dependent 4-fold increase in production of IL-5 and expression of integrin alpha(4)beta(7). Conclusions: PN induces RALDH2 in human APCs by signaling through the TLR1/TLR2 heterodimer. This leads to production of RA, which acts on TH cells to induce IL-5 and gut-homing integrin. RALDH2 induction by PN in APCs and RA-promoted T(H)2 differentiation could be an important factor determining allergic responses to peanut.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据