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

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dc.creatorGabriel Augusto Oliveira Lopes
dc.creatorBraulio Henrique Freire Lima
dc.creatorCamila Simões Freitas
dc.creatorAndiara Cardoso Peixoto
dc.creatorFrederico Marianetti Soriani
dc.creatorGeovanni Dantas Cassali
dc.creatorBernhard Ryffel
dc.creatorMauro Martins Teixeira
dc.creatorFabiana Simão Machado
dc.creatorRemo Castro Russo
dc.date.accessioned2026-01-06T21:08:33Z
dc.date.issued2024-10-01
dc.identifier.doihttps://doi.org/10.1002/iid3.70042
dc.identifier.issn2050-4527
dc.identifier.urihttps://hdl.handle.net/1843/1299
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofImmunity, inflammation and disease
dc.rightsAcesso aberto
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCélulas Mieloides
dc.subjectGenetica
dc.subject.otherCD11c
dc.subject.otherDendritic cell
dc.subject.otherFibrosis
dc.subject.otherMacrophage
dc.subject.otherMyeloid
dc.subject.otherα‐X integrin
dc.titleOpposite effects of systemic and local conditional CD11c+ myeloid cell depletion during bleomycin-induced inflammation and fibrosis in mice
dc.typeArtigo de periódico
local.citation.epage22
local.citation.issue11
local.citation.spage1
local.citation.volume12
local.description.resumoRationale: elevated 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. Objective: we aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin-induced pulmonary fibrosis in mice. Methods: we 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. Results: fourteen 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. Conclusion: systemic 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.
local.publisher.countryBrasil
local.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
local.publisher.initialsUFMG
local.subject.cnpqCIENCIAS BIOLOGICAS::GENETICA
local.url.externahttps://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70042

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