Evidence map›Paper›PMID 39582275›Full record

ArticleImmunity, inflammation and disease2024

Opposite effects of systemic and local conditional CD11c+ myeloid cell depletion during bleomycin-induced inflammation and fibrosis in mice.

Gabriel Augusto Oliveira Lopes, Braulio Henrique Freire Lima, Camila Simões Freitas, Andiara Cardoso Peixoto, Frederico Marianetti Soriani, Geovanni Dantas Cassali, Bernhard Ryffel, Mauro Martins Teixeira, Fabiana Simão Machado, Remo Castro Russo

Abstract read
In one paragraph

Article in Immunity, inflammation and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Gabriel Augusto Oliveira LopesLaboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Braulio Henrique Freire LimaLaboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Camila Simões FreitasLaboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Andiara Cardoso PeixotoLaboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Frederico Marianetti SorianiDepartment of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Geovanni Dantas CassaliDepartment of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Bernhard RyffelExperimental and Molecular Immunology and Neurogenetics, University of Orleans, CNRS UMR7355, Orleans, France.
Mauro Martins TeixeiraDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Fabiana Simão MachadoLaboratory of Immunoregulation of Infectious Diseases, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Remo Castro RussoLaboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.ORCID 0000-0002-1715-3834

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico No.309810/2017-5Conselho Nacional de Desenvolvimento Científico e Tecnológico No.312839/2020-0Conselho Nacional de Desenvolvimento Científico e Tecnológico No.313839/2023-9Conselho Nacional de Desenvolvimento Científico e Tecnológico No.422260/2016-9Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Programa CAPES-PrInt/UFMG edital 05/2022European Regional Development Fund FEDERN°2024-00012066Exposome&InflamFundação de Amparo à Pesquisa do Estado de Minas Gerais No. APQ-02571-21Fundação de Amparo à Pesquisa do Estado de Minas Gerais No. RED-00031-21Studium Loire Valley-Institute for Advanced Studies LE STUDIUM Visiting Researcher/ARD CVL Biopharmace
6 · The paper itself

Abstract

rationaleElevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen-presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood.

objectiveWe aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin-induced pulmonary fibrosis in mice.

methodsWe used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c-DTR-Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin-induced lung inflammation and fibrosis.

resultsFourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c-DTR-Tg mice protected against bleomycin-induced mortality and pulmonary fibrosis compared to wild-type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis-related mRNAs (Collagen-1α1 and α-SMA). Increased anti-inflammatory cytokine IL-10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL-1β, with lung hyper-inflammation and early fibrosis development.

conclusionSystemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality.

Indexed as

BleomycinCD11c AntigenDendritic CellsMice, TransgenicMyeloid CellsPulmonary FibrosisAnimalsDisease Models, AnimalInflammationLungMacrophagesMiceMice, Inbred C57BLPneumoniaBleomycinCD11c AntigenCD11cdendritic cellfibrosismacrophagemyeloidα‐X integrin

Identifiers

PMID39582275
PMCPMC11586507

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.