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J Exp Med. 2018 Nov 5;215(11):2778-2795. doi: 10.1084/jem.20181468. Epub 2018 Oct 3.

Neutrophils instruct homeostatic and pathological states in naive tissues.

Author information

1
Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
2
Singapore Immunology Nework (SIgN), A*STAR, Biopolis, Singapore.
3
Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
4
Department of Immunology, University of Toronto, Canada.
5
University Duisburg-Essen, University Hospital, Institute for Experimental Immunology and Imaging, Essen, Germany.
6
Institute for Cardiovascular Prevention, Ludwig-Maximilians University, Munich, Germany.
7
Dept. of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.
8
Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan.
9
German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
10
Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
11
Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain ahidalgo@cnic.es.

Abstract

Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics. By focusing in two particular tissues, the intestine and the lungs, we find that neutrophils infiltrating the intestine are engulfed by resident macrophages, resulting in repression of Il23 transcription, reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches. In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature influenced circadian transcription in the lungs. Neutrophil-influenced transcripts in this organ were associated with carcinogenesis and migration. Consistently, we found that neutrophils dictated the diurnal patterns of lung invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet of neutrophil biology that supports organ function, but can also instigate pathological states.

PMID:
30282719
PMCID:
PMC6219739
[Available on 2019-05-05]
DOI:
10.1084/jem.20181468

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