TY - JOUR
T1 - Neutrophils instruct homeostatic and pathological states in naive tissues
AU - Casanova-Acebes, Maria
AU - Nicolas-Avila, Jose A.
AU - Li, Jackson LiangYao
AU - Garcia-Silva, Susana
AU - Balachander, Akhila
AU - Rubio-Ponce, Andrea
AU - Weiss, Linnea A.
AU - Adrover, Jose M.
AU - Burrows, Kyle
AU - A-Gonzalez, Noelia
AU - Ballesteros, Ivan
AU - Devi, Sapna
AU - Quintana, Juan A.
AU - Crainiciuc, Georgiana
AU - Leiva, Magdalena
AU - Gunzer, Matthias
AU - Weber, Christian
AU - Nagasawa, Takashi
AU - Soehnlein, Oliver
AU - Merad, Miriam
AU - Mortha, Arthur
AU - Ng, Lai Guan
AU - Peinado, Hector
AU - Hidalgo, Andres
PY - 2018/11/5
Y1 - 2018/11/5
N2 - 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.
AB - 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.
KW - HEMATOPOIETIC STEM-CELLS
KW - ROR-GAMMA-T
KW - BONE-MARROW
KW - FLUORESCENT PROTEIN
KW - P-SELECTIN
KW - HETEROGENEITY
KW - PHAGOCYTOSIS
KW - GRANULOCYTES
KW - MAINTENANCE
KW - MACROPHAGES
U2 - 10.1084/jem.20181468
DO - 10.1084/jem.20181468
M3 - Article
C2 - 30282719
SN - 0022-1007
VL - 215
SP - 2778
EP - 2795
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -