Temblay Jeffrey N, Bertelli Eugenio, Arques Juan L, Regoli Mari, Nicoletti Claudio
Gastrointestinal Biology and Health Program, Institute of Food Research, Norwich, United Kingdom.
J Allergy Clin Immunol. 2007 Sep;120(3):659-65. doi: 10.1016/j.jaci.2007.04.044. Epub 2007 Jun 28.
Dendritic cells (DCs) play a pivotal role in antigen presentation and regulation of immune responses; however, their involvement in food allergy remains to be fully understood.
Our aim was to investigate T(H)1-T(H)2 reciprocal regulation of DCs' function in the gut and systemic immune system and its effect on food allergy in mice with different susceptibility to food allergy.
Freshly isolated CD11c(+)B220(-)DCs from peanut-sensitized allergy-susceptible C3H/HeJ and allergy-resistant Balb/c mice were cultured to determine levels of IL-12p70 produced in the presence of cytokines, including IL-4. Systemic levels of IL-12 were assessed in vivo after antigen challenge with or without IL-4. Targeted oral delivery of microencapsulated neutralizing anti-IL-12 antibody to Peyer patches (PPs) was performed in Balb/c before administration of each sensitizing dose.
Peyer patch-DCs but not splenic DCs from sensitized C3H/HeJ but not Balb/c mice produced less IL-4-dependent IL-12p70. In vivo data confirmed this was restricted to the gut immune system, and it was not linked to reduced expression of IL-4 receptor or the lack of functional Toll-like receptor 4; instead, IL-4 failed to inhibit IL-10 production by PP-DCs, a pathway critically involved in IL-4-dependent production of IL-12p70. Finally, neutralization of IL-12 within PPs by specific antibody during antigen presentation significantly increased Balb/c susceptibility to food allergy.
Reciprocal T(H)1-T(H)2 control of DCs' function within the inductive site of the gut immune system is altered in food allergy.
Production of IL-12p70 by PP-DCs during antigen presentation is critical for the development of food allergy.
树突状细胞（DCs）在抗原呈递和免疫反应调节中起关键作用；然而，它们在食物过敏中的作用仍有待充分了解。
我们的目的是研究在对食物过敏易感性不同的小鼠中，肠道和全身免疫系统中DCs功能的Th1-Th2相互调节及其对食物过敏的影响。
从花生致敏的过敏易感C3H/HeJ小鼠和过敏抗性Balb/c小鼠中新鲜分离出CD11c(+)B220(-)DCs，进行培养以确定在包括IL-4在内的细胞因子存在下产生的IL-12p70水平。在用或不用IL-4进行抗原攻击后，在体内评估IL-12的全身水平。在每次致敏剂量给药前，对Balb/c小鼠进行靶向口服微囊化中和抗IL-12抗体至派尔集合淋巴结（PPs）。
致敏的C3H/HeJ小鼠而非Balb/c小鼠的派尔集合淋巴结DCs而非脾DCs产生较少的IL-4依赖性IL-12p70。体内数据证实这仅限于肠道免疫系统，且与IL-4受体表达降低或功能性Toll样受体4缺乏无关；相反，IL-4未能抑制PP-DCs产生IL-10，这是IL-4依赖性产生IL-12p70的关键途径。最后，在抗原呈递期间通过特异性抗体中和PPs内的IL-12显著增加了Balb/c小鼠对食物过敏的易感性。
在食物过敏中，肠道免疫系统诱导部位内DCs功能的Th1-Th2相互控制发生改变。
抗原呈递期间PP-DCs产生IL-12p70对食物过敏的发展至关重要。
