The atypical chemokine receptor ACKR2 drives pulmonary fibrosis by tuning influx of CCR2+ and CCR5+ IFNγ-producing γδT cells in mice

American Journal of Physiology. Lung Cellular and Molecular Physiology
Remo C RussoMauro M Teixeira

Abstract

Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical chemokine receptors (ACKRs) bind, internalize, and degrade chemokines, tuning homeostasis and immune responses. ACKR2 recognizes and decreases the levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. The purpose of the study was to investigate the role of ACKR2 in the context of pulmonary fibrosis. The effects of ACKR2 expression and deficiency during inflammation and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras, and antibody-mediated leukocyte depletion. ACKR2 was upregulated acutely in response to bleomycin and normalized over time. ACKR2-/- mice showed reduced lethality and lung fibrosis. Bone marrow chimeras showed that lethality and fibrosis depended on ACKR2 expression in pulmonary resident (nonhematopoietic) cells but not on leukocytes. ACKR2-/- mice exhibited decreased expression of tissue-remodeling genes, reduced leukocyte influx, pulmonary injury, and dysfunction. ACKR2-/- mice had early increased levels of CCL5, CCL12, CCL17, and IFNγ and an increased number of CCR2+ and CCR5+ IFNγ-producin...Continue Reading

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Citations

Jan 9, 2020·Future Microbiology·Nathália Lso MalaccoFrederico M Soriani
Jan 30, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Luciana P TavaresRemo C Russo
Aug 20, 2019·Metabolomics : Official Journal of the Metabolomic Society·Chan SeoMan-Jeong Paik
Jan 29, 2019·Frontiers in Cellular and Infection Microbiology·Nathália Luísa Sousa de Oliveira MalaccoFrederico Marianetti Soriani
Oct 31, 2020·Frontiers in Immunology·Matheus Silverio MattosRemo Castro Russo
Nov 6, 2020·ImmunoTargets and Therapy·Kevin M C LeeJohn A Hamilton
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Luiz Alexandre Medrado de BarcellosVanessa Pinho
Apr 4, 2021·Cancers·Andy ChevignéMartyna Szpakowska

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Methods Mentioned

BETA
PCR
FACS
ELISA
bronchoalveolar lavage

Software Mentioned

BD FACSDiva
Buxco
INNOCHEM
GraphPad Prism

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