Division of Allergy and Immunology, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Chongqing Health Center for Women and Children, Chongqing Shi, China.
Clin Exp Allergy. 2017 Dec;47(12):1574-1585. doi: 10.1111/cea.13013. Epub 2017 Oct 10.
Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis.
We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice.
C57BL/6 WT, tlr4 and IL10 mice were exposed to LPS, and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE, and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca -mobilization and the expression of FcεRI on peritoneal MCs were quantitated.
We show that LPS exposure of C57BL/6 WT mice constraints IgE-MC-mediated reactions. LPS-induced suppression of IgE-MC-mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression.
CONCLUSIONS & CLINICAL RELEVANCE: Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10 pathway may be used as a therapeutic approach to prevent adverse IgE-mediated reactions.
临床和实验分析已经确定 IgE/FcεRI/肥大细胞在促进 IgE 介导的过敏反应中起核心作用。最近来自人类研究的数据表明，细菌感染可以改变过敏反应的易感性。
我们研究了 LPS 暴露对诱导小鼠 IgE-肥大细胞（MC）介导反应的影响。
C57BL/6 WT、tlr4 和 IL10 小鼠暴露于 LPS 后，测量血清细胞因子（TNF 和 IL-10）。随后用抗 IgE 处理小鼠，定量测定被动 IgE 介导的过敏反应、MC 活化、Ca 动员和腹腔 MC 上 FcεRI 的表达。
我们表明 LPS 暴露于 C57BL/6 WT 小鼠限制了 IgE-MC 介导的反应。LPS 诱导的 IgE-MC 介导反应的抑制作用依赖于 TLR-4，并与全身 IL-10 水平升高、MC 表面 FcεRI 表达降低和对 IgE 激活的敏感性丧失有关。值得注意的是，MC 对 IgE 的敏感性在 LPS 诱导的脱敏作用是短期的，在 48 小时内重新建立，这与 MC 上 FcεRI 的表达再现有关。机制分析表明，IL-10 在 LPS 介导的 MC FcεRI 表面表达下调中起作用。
总之，这些研究表明，LPS 诱导的 IL-10 促进 MC 表面 FcεRI 表达的下调，并导致小鼠对 IgE 介导的反应脱敏。这些研究表明，靶向 LPS-TLR-4-IL-10 途径可能作为预防不良 IgE 介导反应的治疗方法。
