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导管巨噬细胞在哺乳期乳腺的免疫景观中占优势。

Ductal Macrophages Predominate in the Immune Landscape of the Lactating Mammary Gland.

机构信息

IHAP, Université de Toulouse, ENVT, Institut National de la Recherche Agronomique et Environnement (INRAE), Toulouse, France.

出版信息

Front Immunol. 2021 Oct 20;12:754661. doi: 10.3389/fimmu.2021.754661. eCollection 2021.

DOI:10.3389/fimmu.2021.754661
PMID:34745127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8564477/
Abstract

The mammary gland is unique in female mammals. Mammary tissue undergoes development and remodeling during lactation, a stage associated with high susceptibility to bacterial infections, inducing an inflammatory condition called mastitis. Although the immune response of the mammary gland has been the subject of intense research to improve prevention and treatment efficacy, the precise definition of its immune composition at this particular physiological stage is still missing. We combined single-cell RNA-Seq, flow cytometry, and three-dimensional confocal microscopy techniques to characterize the immune landscape of lactating murine mammary tissue. Macrophages dominated the immune cell repertoire and could be subdivided into at least two subsets: ductal and stromal macrophages. Ductal macrophages represented approximately 80% of the total CD45 immune cells and co-expressed F4/80 and CD11c, with high levels of MHC class II molecules. They were strategically poised below the alveolar basal cells in contact with the myoepithelial cell network. Adaptive T and B lymphocytes were remarkably less numerous at this stage, which could explain the limited efficacy of vaccination against mastitis. These results support the view that new strategies to increase mammary immunity and prevent mastitis should be devised.

摘要

乳腺在雌性哺乳动物中是独一无二的。乳腺组织在哺乳期经历发育和重塑,这一阶段易受细菌感染,导致乳腺炎等炎症状态。尽管乳腺的免疫反应一直是提高预防和治疗效果的研究热点,但在这个特定的生理阶段,其免疫成分的精确定义仍然缺失。我们结合单细胞 RNA-Seq、流式细胞术和三维共聚焦显微镜技术,对哺乳期小鼠乳腺组织的免疫图谱进行了表征。巨噬细胞主导了免疫细胞组成,可进一步细分为至少两个亚群:导管和基质巨噬细胞。导管巨噬细胞约占总 CD45 免疫细胞的 80%,共表达 F4/80 和 CD11c,高水平表达 MHC Ⅱ类分子。它们位于肺泡基底细胞下方,与肌上皮细胞网络接触。在这个阶段,适应性 T 和 B 淋巴细胞的数量显著较少,这可以解释针对乳腺炎的疫苗接种效果有限。这些结果支持这样的观点,即应该设计新的策略来增强乳腺免疫力并预防乳腺炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/8905bf6f1e90/fimmu-12-754661-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/5cd80cd64076/fimmu-12-754661-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/3889b9757783/fimmu-12-754661-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/3a467127e00b/fimmu-12-754661-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/8905bf6f1e90/fimmu-12-754661-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/5cd80cd64076/fimmu-12-754661-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/3889b9757783/fimmu-12-754661-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/3a467127e00b/fimmu-12-754661-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/8564477/8905bf6f1e90/fimmu-12-754661-g004.jpg

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Single-Cell Resolution Three-Dimensional Imaging of Intact Organoids.
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