哮喘联盟

   摘要
   哮喘是一种常见的炎症性疾病，涉及天然免疫和获得性免疫之间的相互作用。我们发现，抗菌的天然免疫蛋白肽聚糖识别蛋白（Pglyrp）1参与了过敏性哮喘的发病过程。采用屋尘螨（HDM）致敏后，Pglyrp1(-/-)小鼠出现的哮喘，严重程度轻于野生型（WT）小鼠的哮喘。与WT小鼠相比，HDM 致敏的Pglyrp1(-/-)小鼠支气管高反应性（肺气道阻力）下降；支气管肺泡灌洗液和肺组织内嗜酸性粒细胞、中性粒细胞、淋巴细胞和巨噬细胞下降；支气管、细支气管和肺动静脉周围肺组织炎症细胞浸润也改善；肺重构（产粘蛋白的杯状细胞过度增生和化生、平滑肌细胞肥大和纤维化）得到改善；肺组织内IgE、嗜酸粒细胞亲合素（eotaxin）、IL-4、IL-5和IL-17下降；肺内Th2和Th17细胞数量和其标志物表达也下降。Pglyrp1(-/-)小鼠对哮喘的敏感性下降，其机制可能与肺内CD8α(+)β(+)和CD8α(+)β(-)类浆细胞性树突状细胞（pDC）产生和活化增加以及调节性T细胞（Treg）聚集和活性增加有关。HDM致敏的Pglyrp1(-/-)小鼠，在体去除pDC能逆转这些动物较低的哮喘敏感性，产生的哮喘较野生型小鼠的哮喘表现型更严重。因此，在Pglyrp1(-/-)小鼠，通过上调肺内pDC和Treg细胞可有效控制过敏性哮喘，而在野生型小鼠中，Pglyrp1是一个促炎因子，能减少pDC和Treg细胞，增加致哮喘的Th2和Th17反应。阻断肺内Pglyrp1或增加肺内pDC则有助于预防和治疗哮喘。
 

（刘国梁 审校）
J Immunol. 2013 Feb 18. [Epub ahead of print]
 

Peptidoglycan Recognition Protein 1 Enhances Experimental Asthma by Promoting Th2 and Th17 and Limiting Regulatory T Cell and Plasmacytoid Dendritic Cell Responses.
 
Park SY, Jing X, Gupta D, Dziarski R.

Source
Indiana University School of Medicine-Northwest, Gary, IN 46408.

Abstract 
Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity. We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1(-/-) mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDM-sensitized Pglyrp1(-/-) mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1(-/-) mice to asthma was increased generation and activation of CD8α(+)β(+) and CD8α(+)β(-) plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1(-/-) mice reversed the low responsive asthmaphenotype of Pglyrp1(-/-) mice to resemble the more severe WT phenotype. Thus, Pglyrp1(-/-) mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma.
 

J Immunol. 2013 Feb 18. [Epub ahead of print]