BibTex format
@article{Sanchez-Garcia:2025:10.1038/s41590-025-02301-9,
author = {Sanchez-Garcia, MA and Sadiku, P and Ortmann, BM and Wit, N and Negishi, Y and Coelho, P and Zhang, A and Pednekar, C and Howden, AJM and Griffith, DM and Seear, R and Kindrick, JD and Mengede, J and Cooper, G and Morrison, T and Watts, ER and Shimeld, BT and Reyes, L and Mirchandani, AS and Arienti, S and Xu, X and Thomson, A and Brenes, AJ and Turton, HA and Dowey, R and Hull, RC and Davidson-Smith, H and McLaren, A and Deans, A and Choudhury, G and Doverman, K and Hope, D and Vick, O and Woodhead, A and Petrie, I and Green, S and Rzechorzek, NM and Turtle, L and Openshaw, PJM and Semple, MG and Sproul, D and Baillie, JK and Thompson, AAR and Mole, DR and Von, Kriegsheim A and Whyte, MKB and Mhalanga, MM and Nathan, JA and Walmsley, SR},
doi = {10.1038/s41590-025-02301-9},
journal = {Nature Immunology},
title = {Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity},
url = {http://dx.doi.org/10.1038/s41590-025-02301-9},
volume = {26},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The long-term impact of systemic hypoxia resulting from acute respiratory distress syndrome (ARDS) on the function of short-lived innate immune cells is unclear. We show that patients 3–6 months after recovering from ARDS have persistently impaired circulating neutrophil effector functions and an increased susceptibility to secondary infections. These defects are linked to a widespread loss of the activating histone mark H3K4me3 in genes that are crucial for neutrophil activities. By studying healthy volunteers exposed to altitude-induced hypoxemia, we demonstrate that oxygen deprivation alone causes this long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal that persistent loss of H3K4me3 originates in proNeu and preNeu progenitors within the bone marrow and is linked to N-terminal histone 3 clipping, which removes the lysine residue for methylation. Thus, we present new evidence that systemic hypoxia initiates a sustained maladaptive reprogramming of neutrophil immunity by triggering histone 3 clipping and H3K4me3 loss in neutrophil progenitors.
AU - Sanchez-Garcia,MA
AU - Sadiku,P
AU - Ortmann,BM
AU - Wit,N
AU - Negishi,Y
AU - Coelho,P
AU - Zhang,A
AU - Pednekar,C
AU - Howden,AJM
AU - Griffith,DM
AU - Seear,R
AU - Kindrick,JD
AU - Mengede,J
AU - Cooper,G
AU - Morrison,T
AU - Watts,ER
AU - Shimeld,BT
AU - Reyes,L
AU - Mirchandani,AS
AU - Arienti,S
AU - Xu,X
AU - Thomson,A
AU - Brenes,AJ
AU - Turton,HA
AU - Dowey,R
AU - Hull,RC
AU - Davidson-Smith,H
AU - McLaren,A
AU - Deans,A
AU - Choudhury,G
AU - Doverman,K
AU - Hope,D
AU - Vick,O
AU - Woodhead,A
AU - Petrie,I
AU - Green,S
AU - Rzechorzek,NM
AU - Turtle,L
AU - Openshaw,PJM
AU - Semple,MG
AU - Sproul,D
AU - Baillie,JK
AU - Thompson,AAR
AU - Mole,DR
AU - Von,Kriegsheim A
AU - Whyte,MKB
AU - Mhalanga,MM
AU - Nathan,JA
AU - Walmsley,SR
DO - 10.1038/s41590-025-02301-9
PY - 2025///
SN - 1529-2908
TI - Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity
T2 - Nature Immunology
UR - http://dx.doi.org/10.1038/s41590-025-02301-9
UR - https://www.nature.com/articles/s41590-025-02301-9
VL - 26
ER -