AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 投稿方向-刊鹿论文编译

Calprotectin-g the Lung during Type 2 Allergic Airway Inflammation

Abstract:

Asthma is a chronic, complex pulmonary disease that affects z300 million people worldwide. This multifactorial, heterogeneous disorder is characterized by airflow obstruction and airway inflammation, and encompasses various phenotypes (observable characteristics) and endotypes (biological mechanisms of disease). Generally, asthma is classified as eosinophilic or noneosinophilic based on airway or peripheral blood cellular profiles, but marked heterogeneity exists throughout the entire spectrum of the disease and is most pronounced in the subset of severe disease (1). Understanding the complex immune pathways and other diseasemodulating factors (i.e., microbiome, metabolome, and genetics) is necessary to refine asthma endotypes and to improve treatment strategies for patients with this disease. Eosinophilic, atopic asthma is driven by T-helper cell type 2 (Th2) responses (IL-4, IL-5, and IL-3) to inhaled allergens. However, eosinophilic airway inflammation is also present in nonatopic asthma (1). Although allergic asthma and eosinophil-dominant asthma are the most frequent and often effectively managed subgroups, z10–15% of individuals with asthma have severe corticosteroid-refractory disease with a noneosinophilic inflammatory response and experience persistent symptoms and frequent exacerbations. Noneosinophilic or type 2 low asthma is diverse and consists of disease with neutrophil-dominant inflammation resulting from type 1 and type 17 cytokines, mixed granulocytic inflammation with concurrent allergic and nonallergic mechanisms, or paucigranulocytic inflammation (2). We have made progress in understanding the heterogeneity of the immunological responses in asthma, but our knowledge of the underlying mechanisms of severe, noneosinophilic asthma is still limited. Experimental models to mimic noneosinophilic or mixed disease phenotypes have emerged and are likely to be essential for developing a better understanding of this heterogeneous disease (3–5). Calprotectin is a heterodimeric complex of S100A8 (MRP8 [myeloid-related protein 8]) and S100A9 (MRP14) and is associated with a number of inflammatory diseases, including inflammatory bowel disease, arthritis, psoriasis, and pulmonary infection (6). These innate immune proteins are both bacteriostatic and proinflammatory in nature (7). Specifically, S100 proteins, like these, comprise a group of damage-associated molecular pattern molecules that bind to and activate TLR4 (Toll-like receptor 4) and RAGE (receptor for advanced glycation end products), which has been implicated in type 2 allergic airway disease in mice (8, 9). It is known that S100A8 and S100A9 are secreted in a disease-specific manner mainly from neutrophils and macrophages, but few mechanistic studies have focused on defining the role of these proteins during inflammation. In the lung, both clinical and animal findings have linked calprotectin with asthma. S100A8 and S100A9 are upregulated in individuals with asthma compared with those without asthma and are associated with more severe, uncontrolled disease phenotypes (10–13). Specifically, Lee and colleagues found that S100A9 levels were higher in sputum from patients with severe asthma and neutrophil-dominant inflammation compared than in sputum from eosinophil-dominant and paucigranulocytic groups (12, 13). Furthermore, S100A9 levels significantly correlated with the percentage of neutrophils in the sputum (13). These data suggest that S100A9 may initiate and amplify neutrophilic inflammation in patients with uncontrolled, severe asthma. In experimental animal models of asthma, the role of calprotectin is more ambiguous. Some studies demonstrated that exogenous treatment of S100A8 and S100A9 reduced Th2-mediated responses after ovalbumininduced allergic airway inflammation (14, 15), whereas others using neutralizing antibodies for S100A8 and S100A9 showed that calprotectin promoted disease in a mixed allergen model (16). Together, these studies show that the role of calprotectin may differ based on the inflammatory context in the asthmatic lung. In this issue of the Journal, Palmer and colleagues (pp. 459–468) examine the role of S100A9/calprotectin in allergic airway inflammation in mice (17). Although calprotectin is implicated in the pathogenesis of inflammatory diseases by functioning as a ligand for TLR4 and RAGE, this study elucidates an alternative and antiinflammatory mechanism by which S100A9 influences innate and adaptive immune responses (Figure 1). Using the Alternaria alternata model of type 2 high allergic airway inflammation, the authors found that calprotectin-deficient mice (S100A9) had worsened disease as evidenced by increased airway eosinophilia, type 2 helper T cell (Th2) activation, and airway resistance and elastance responses to methacholine challenge. Specifically, calprotectin restricted the number of IL-13/IL-5–producing CD4 T cells in the lung, but not by altering the amount of group 2 innate lymphoid cells in response to A. alternata. Furthermore, the authors demonstrate that increased allergic airway inflammation in calprotectin-deficient mice results from the inability of T regulatory cells to control Th2 responses, identifying a novel role for S100A9 in regulating CD4 T-cell responses in the context of asthma. These data also support a central role for antigen-specific Th2 cells in promoting airway hyperresponsiveness. Although their data are consistent with previous findings suggesting that calprotectin protects against allergic airway inflammation (14, 15), their work significantly advances the field by providing mechanistic insight into a physiological and immunological role for calprotectin in asthma. S100A8/S100A9 currently serves as a candidate biomarker and predictive indicator of therapeutic responsiveness in various inflammatory diseases (6). However, the localization and timing of calprotectin induction during disease are still unclear. In the lung, S100A8 was found to be expressed by neutrophils and macrophages and upregulated during acute allergic inflammation (16). Similarly, S100A9 was shown to be localized to neutrophils and bronchial epithelial cells in the airway during neutrophil-dominant allergic

Author Listing： Michelle L Manni;John F Alcorn

Volume： 61

Pages： 405 - 407

DOI： 10.1165/rcmb.2019-0125ED

Language： English

Journal： American Journal of Respiratory Cell and Molecular Biology

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

AM J RESP CELL MOL

影响因子：5.9

是否综述期刊：否

是否OA：否

是否预警：不在预警名单内

发行时间：1989

ISSN：1044-1549

发刊频率：Monthly

收录数据库：SCIE/Scopus收录

出版国家/地区：UNITED STATES

出版社：American Thoracic Society

期刊介绍

The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.

《美国呼吸细胞和分子生物学杂志》发表的论文报告了肺生物学领域的重要和原始观察结果。该杂志的重点包括但不限于肺细胞和分子的细胞学、生物化学、分子学、发育学、遗传学和免疫学研究。

年发文量	96
国人发稿量	17
国人发文占比	17.71%
自引率	5.1%
平均录取率	较难
平均审稿周期	一般,3-8周
版面费	-
偏重研究方向	生物-呼吸系统
期刊官网	https://www.atsjournals.org/journal/ajrcmb
投稿链接	https://mc.manuscriptcentral.com/ajrcmb

质量指标占比

研究类文章占比	OA被引用占比	撤稿占比	出版后修正文章占比
96.88%	12.42%	0.00%	3.13%

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时间	预警情况
2024年02月发布的2024版	不在预警名单中
2023年01月发布的2023版	不在预警名单中
2021年12月发布的2021版	不在预警名单中
2020年12月发布的2020版	不在预警名单中

JCR分区 WOS分区等级：Q1区

版本	按学科	分区
WOS期刊SCI分区 WOS期刊SCI分区是指SCI官方（Web of Science）为每个学科内的期刊按照IF数值排序，将期刊按照四等分的方法划分的Q1-Q4等级，Q1代表质量最高，即常说的1区期刊。（2021-2022年最新版）
	CELL BIOLOGY	Q1
	RESPIRATORY SYSTEM	Q1
	BIOCHEMISTRY & MOLECULAR BIOLOGY	Q1

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分区表升级版（试行）的优势：一是论文层级的主题体系既能体现学科交叉特点，又可以精准揭示期刊载文的多学科性；二是采用“期刊超越指数”替代影响因子指标，解决了影响因子数学性质缺陷对评价结果的干扰。整体而言，分区表升级版（试行）突破了期刊评价中学科体系构建、评价指标选择等瓶颈问题，能够更为全面地揭示学术期刊的影响力，为科研评价“去四唯”提供解决思路。相关研究成果经过国际同行的认可，已经发表在科学计量学领域国际重要期刊。

《2019年中国科学院文献情报中心期刊分区表升级版（试行）》首次将社会科学引文数据库（SSCI）期刊纳入到分区评估中。升级版分区表（试行）设置了包括自然科学和社会科学在内的18个大类学科。基础版和升级版（试行）将过渡共存三年时间，推测在此期间各大高校和科研院所仍可能会以基础版为考核参考标准。提示：中科院分区官方微信公众号“fenqubiao”仅提供基础版数据查询，暂无升级版数据，请注意区分。

中科院分区查看说明

版本	大类学科	小类学科	Top期刊	综述期刊
	医学 1区	CELL BIOLOGY 细胞生物学 2区 RESPIRATORY SYSTEM 呼吸系统 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	是
2021年12月基础版	医学 2区	CELL BIOLOGY 细胞生物学 3区 RESPIRATORY SYSTEM 呼吸系统 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	否
2021年12月升级版	医学 1区	CELL BIOLOGY 细胞生物学 2区 RESPIRATORY SYSTEM 呼吸系统 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	是
2020年12月旧的升级版	医学 1区	CELL BIOLOGY 细胞生物学 2区 RESPIRATORY SYSTEM 呼吸系统 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	是
2022年12月最新升级版	医学 2区	CELL BIOLOGY 细胞生物学 2区 RESPIRATORY SYSTEM 呼吸系统 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	否