Department of Otorhinolaryngology, Seoul National University College of Medicine, Chongno-gu, Seoul, Korea.
Allergy. 2012 Apr;67(4):502-9. doi: 10.1111/j.1398-9995.2011.02782.x. Epub 2012 Jan 19.
Nasopharynx-associated lymphoid tissue (NALT) serves as an important inductive site for mucosal immunity in the upper respiratory tract. Despite its importance in the mucosal immune system, little is known regarding the role of NALT in airway allergic immune responses. We aimed to elucidate the role of NALT in the induction of upper airway allergic responses in a mouse model.
Inhibitor of DNA binding/differentiation 2 (Id2)(-/-) and Id2(+/-) mice was exposed to the ovalbumin (OVA)-induced allergic rhinitis model, because the former resulted in the NALT deficiency. The allergic parameters, such as allergic symptoms, serum OVA-specific immunoglobulin E (IgE) levels, eosinophil infiltration, and cytokine profiles in the nasal mucosa, were compared between Id2(-/-) and Id2(+/-) groups.
NALT-null, Id2(-/-) mice displayed significantly lower allergic responses compared with Id2(+/-) mice, as demonstrated by lower levels of allergic symptoms, serum OVA-specific IgE, eosinophilic infiltration, and local Th2 cytokine transcriptions. To determine which of two factors, that is, the absence of NALT or the alteration of immunocompetent cell populations caused by the Id2 deficiency, has a larger effect on the attenuated allergic immune responses in Id2(-/-) mice, lethally irradiated Id2(-/-) mice were engrafted with C57BL/6 wild-type bone marrow cells and showed still significantly lower allergic immune responses compared with equally treated Id2(+/-) mice. In addition, IgE class switch recombination-associated molecules, such as ε immunoglobulin heavy-chain germline gene transcript, ε mRNA, and activation-induced cytidine deaminase mRNA, were detected in NALT from OVA-sensitized wild-type mice.
These results show the critical role of NALT for the induction of allergic responses in the upper airway at least in part by means of class switching to IgE in situ.
鼻咽相关淋巴组织 (NALT) 是上呼吸道黏膜免疫的重要诱导部位。尽管 NALT 在黏膜免疫系统中很重要，但人们对其在上呼吸道变应性免疫反应中的作用知之甚少。我们旨在阐明 NALT 在小鼠模型中诱导上呼吸道变应性反应中的作用。
抑制 DNA 结合/分化 2（Id2）（-/-）和 Id2（+/-）小鼠暴露于卵清蛋白（OVA）诱导的变应性鼻炎模型中，因为前者导致 NALT 缺乏。比较 Id2（-/-）和 Id2（+/-）组之间的变应性参数，如过敏症状、血清 OVA 特异性免疫球蛋白 E（IgE）水平、嗜酸性粒细胞浸润和鼻黏膜细胞因子谱。
NALT 缺失的 Id2（-/-）小鼠与 Id2（+/-）小鼠相比，过敏反应明显降低，表现为过敏症状、血清 OVA 特异性 IgE、嗜酸性粒细胞浸润和局部 Th2 细胞因子转录水平降低。为了确定两种因素中的哪一种，即 NALT 的缺失或 Id2 缺乏引起的免疫活性细胞群体的改变，对 Id2（-/-）小鼠减弱的变应性免疫反应有更大的影响，致死性照射的 Id2（-/-）小鼠被植入 C57BL/6 野生型骨髓细胞，并与同样处理的 Id2（+/-）小鼠相比，仍显示出明显较低的过敏免疫反应。此外，在 OVA 致敏的野生型小鼠的 NALT 中检测到 IgE 类转换相关分子，如ε免疫球蛋白重链胚系基因转录本、ε mRNA 和激活诱导的胞苷脱氨酶 mRNA。
这些结果表明，NALT 在上呼吸道诱导过敏反应中起关键作用，至少部分是通过原位 IgE 类转换实现的。
