Neutrophils instruct homeostatic and pathological states in naive tissues
Open Access
- 3 October 2018
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 215 (11), 2778-2795
- https://doi.org/10.1084/jem.20181468
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (CRC914-B08, CRC1123-B04)
- MCIU (SAF2012-31142)
- Comunidad de Madrid (S2010/BMD-2314, SAF2013-49662-EXP)
- MCIU (2010-032828, SVP-2014-068595, BES-2013–065550, JCI-2012-14147, JCI-2012-12659, MSCA-IF-EF-748381)
- Canadian Institutes of Health Research (CIHR 388337)
- CNIC
- MCIU (SEV-2015-0505)
- A*Star
- H2020 Program from the EU (MSCA-IF-EF-74838)
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