Bentley J Kelley, Chen Qiang, Hong Jun Young, Popova Antonia P, Lei Jing, Moore Bethany B, Hershenson Marc B
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mich.
J Allergy Clin Immunol. 2014 Dec;134(6):1433-1442. doi: 10.1016/j.jaci.2014.05.029. Epub 2014 Jul 2.
Periostin, a secreted extracellular matrix protein, has been localized to deposits of subepithelial fibrosis in asthmatic patients, and periostin levels have been linked to increases in IL-13.
We hypothesized that periostin is required for airway inflammatory responses to a physiologic aeroallergen, house dust mite (HDM).
We studied F4-F6 B6;129-Postn(tm1Jmol)/J wild-type (Postn(+/+)) and null (Postn(-/-)) mice, as well as C57BL/6 mice treated with either IgM or OC-20 periostin neutralizing antibody. Mice were exposed to 5 doses of HDM intranasally over a 16-day period.
HDM increased airways responsiveness in Postn(+/+) but not Postn(-/-) mice. In addition, HDM-treated C57BL/6 mice injected with OC-20 had lower airways responsiveness than HDM-treated mice injected with IgM. Compared with Postn(+/+) mice, Postn(-/-) mice showed decreases in HDM-induced inflammation and mucous metaplasia, as well as reduced IL-4, IL-25, CD68, Gob5, and periostin mRNA expression. OC-20 antibody produced similar results. HDM exposure increased periostin expression in the airway epithelium, subepithelium, smooth muscle and inflammatory cells. OC-20 blocked the HDM-induced IgE response, and T cells incubated with dendritic cells (DCs) from Postn(-/-) mice or treated with OC-20 showed deficient DNA synthesis and IL-13 responses compared with T cells incubated with wild-type DCs. Finally, adoptive transfer of bone marrow-derived DCs from Postn(+/+) mice was sufficient to promote allergic responses in F6 Postn(-/-) littermates.
In mice, periostin is required for maximal airways hyperresponsiveness and inflammation after HDM sensitization and challenge. Periostin is required for maximal HDM-induced T-cell responses.
骨膜蛋白是一种分泌型细胞外基质蛋白，在哮喘患者的上皮下纤维化沉积物中定位，且骨膜蛋白水平与白细胞介素-13的增加有关。
我们假设骨膜蛋白是气道对生理性气传变应原屋尘螨（HDM）产生炎症反应所必需的。
我们研究了F4 - F6 B6;129 - Postn(tm1Jmol)/J野生型（Postn(+/+)）和缺失型（Postn(-/-)）小鼠，以及用IgM或OC - 20骨膜蛋白中和抗体处理的C57BL/6小鼠。小鼠在16天内鼻内给予5剂HDM。
HDM增加了Postn(+/+)小鼠的气道反应性，但未增加Postn(-/-)小鼠的气道反应性。此外，注射OC - 20的HDM处理的C57BL/6小鼠比注射IgM的HDM处理的小鼠气道反应性更低。与Postn(+/+)小鼠相比，Postn(-/-)小鼠HDM诱导的炎症和黏液化生减少，白细胞介素-4、白细胞介素-25、CD68、Gob5和骨膜蛋白mRNA表达降低。OC - 20抗体产生了类似的结果。HDM暴露增加了气道上皮、上皮下、平滑肌和炎症细胞中的骨膜蛋白表达。OC - 20阻断了HDM诱导的IgE反应，与用野生型树突状细胞（DCs）孵育的T细胞相比，用Postn(-/-)小鼠的DCs孵育或用OC - 20处理的T细胞显示DNA合成和白细胞介素-13反应不足。最后，来自Postn(+/+)小鼠的骨髓源性DCs的过继转移足以促进F6 Postn(-/-)同窝小鼠的过敏反应。
在小鼠中，骨膜蛋白是HDM致敏和激发后最大气道高反应性和炎症所必需的。骨膜蛋白是HDM诱导的最大T细胞反应所必需的。
