Vannella Kevin M, Ramalingam Thirumalai R, Hart Kevin M, de Queiroz Prado Rafael, Sciurba Joshua, Barron Luke, Borthwick Lee A, Smith Allen D, Mentink-Kane Margaret, White Sandra, Thompson Robert W, Cheever Allen W, Bock Kevin, Moore Ian, Fitz Lori J, Urban Joseph F, Wynn Thomas A
Program in Tissue Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Tissue Fibrosis and Repair Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Nat Immunol. 2016 May;17(5):538-44. doi: 10.1038/ni.3417. Epub 2016 Apr 4.
Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.
酸性哺乳动物几丁质酶（AMCase）已知可由过敏原和蠕虫诱导产生，但其在免疫中的作用尚不清楚。利用AMCase缺陷小鼠，我们发现，在过敏原攻击期间，AMCase缺陷会减少2型固有淋巴细胞的数量，但在肺部针对过敏原或蠕虫建立2型炎症时并非必需。相比之下，在用含几丁质的胃肠道线虫巴西日圆线虫和多房棘球绦虫感染后，AMCase缺陷小鼠在2型免疫方面表现出严重缺陷。免疫功能受损与黏液分泌减少以及2型反应标志性基因Il13、Chil3、Retnlb和Clca1的肠道表达降低有关。调节T细胞归巢的CD103(+)树突状细胞在受感染的AMCase缺陷小鼠的肠系膜淋巴结中也减少。因此，AMCase是对肠道线虫产生保护性2型反应的关键启动因子，但在很大程度上对肺部的过敏反应并非必需。
