Human Lung Dendritic Cells: Spatial Distribution and Phenotypic Identification in Endobronchial Biopsies Using Immunohistochemistry and Flow Cytometry

Baharom, Faezzah; Rankin, Gregory; Scholz, Saskia; Pourazar, Jamshid; Ahlm, Clas; Blomberg, Anders; Smed‐Sörensen, Anna

doi:10.3791/55222

Cited by 9 publications

(13 citation statements)

References 22 publications

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“…Additionally, DCs expressing CD1a can be detected in both the epithelium and submucosa of the airways (117, 118, 122). More detailed phenotypic analyses revealed that a subpopulation of CD1c + MDCs express CD1a, mannose receptor (CD206) and langerin (CD207) in human lungs, unlike blood CD1c + MDCs (62, 73, 74, 123).…”

Section: Phenotypic and Functional Characterization Of Human Lung Mnpsmentioning

confidence: 99%

Human Lung Mononuclear Phagocytes in Health and Disease

et al. 2017

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The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)—together termed mononuclear phagocytes (MNPs)—line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naïve T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs may be targeted or modulated in order to attain favorable responses that can improve preventive or treatment strategies against respiratory infections, lung cancer, or lung inflammatory diseases.

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Section: Phenotypic and Functional Characterization Of Human Lung Mnpsmentioning

confidence: 99%

Human Lung Mononuclear Phagocytes in Health and Disease

et al. 2017

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“…As T cells are critical in driving disease progression in sarcoidosis, a more detailed understanding of MNPs that initially activate and modulate T cell responses could provide greater insight on sarcoidosis pathogenesis. We recently developed protocols and characterized MNPs in healthy controls and identified classical, intermediate, and non‐classical monocytes distinguished by their differential expression of CD14 and CD16 as well as CD123 + plasmacytoid DCs (PDCs) and CD1c + and CD141 + myeloid DCs (MDCs) in the respiratory tract . The different subsets of DCs and monocytes have common but also unique features .…”

Section: Introductionmentioning

confidence: 99%

“…1 Sarcoidosis can present with either an acute onset (usually Löfgren's syndrome (LS)) associated with more favorable disease outcome or a Abbreviations: BAL, bronchoalveolar lavage; DC, dendritic cell; EBB, endobronchial biopsy; EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration; LLN, lung-draining lymph node; MNP, mononuclear phagocyte protocols and characterized MNPs in healthy controls and identified classical, intermediate, and non-classical monocytes distinguished by their differential expression of CD14 and CD16 as well as CD123 + plasmacytoid DCs (PDCs) and CD1c + and CD141 + myeloid DCs (MDCs) in the respiratory tract. 5,6 The different subsets of DCs and monocytes have common but also unique features. 7 Classical monocytes circulate in blood and either extravasate into tissues or differentiate into intermediate monocytes and non-classical monocytes.…”

Section: Introductionmentioning

confidence: 99%

Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients

Lepzien

Rankin

Pourazar

et al. 2019

Journal of Leukocyte Biology

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Sarcoidosis is a T‐cell driven inflammatory disease characterized by granuloma formation. Mononuclear phagocytes (MNPs)—macrophages, monocytes, and dendritic cells (DCs)—are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by cytokine production. Granulomas manifest primarily in lungs and lung‐draining lymph nodes (LLNs) but these compartments are less studied compared to blood and bronchoalveolar lavage (BAL). Sarcoidosis can present with an acute onset (usually Löfgren's syndrome (LS)) or a gradual onset (non‐LS). LS patients typically recover within 2 years while 60% of non‐LS patients maintain granulomas for up to 5 years. Here, four LS and seven non‐LS patients underwent bronchoscopy with endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA). From each patient, blood, BAL, endobronchial biopsies (EBBs), and LLN samples obtained by EBUS‐TBNA were collected and MNPs characterized using multicolor flow cytometry. Six MNP subsets were identified at varying frequencies in the anatomical compartments investigated. Importantly, monocytes and DCs were most mature with migratory potential in BAL and EBBs but not in the LLNs suggesting heterogeneity in MNPs in the compartments typically affected in sarcoidosis. Additionally, in LS patients, frequencies of DC subsets were lower or lacking in LLNs and EBBs, respectively, compared to non‐LS patients that may be related to the disease outcome. Our work provides a foundation for future investigations of MNPs in sarcoidosis to identify immune profiles of patients at risk of developing severe disease with the aim to provide early treatment to slow down disease progression.

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“…However, recent studies have generated important insight in this area and Mϕs, monocytes, monocyte-derived DCs (mo-DCs), and bona fide DC subsets have been identified from healthy human respiratory tissues. Figure 1 summarizes the current understanding of the phenotype and distribution of human MNP subsets in respiratory tissues at steady state, as reported ( 41 , 51 , 52 , 57 – 62 ).…”

Section: Human Respiratory Mnpsmentioning

confidence: 94%

“…(B) Distribution of human MNP subsets. Pie charts illustrate broadly pooled data from 21 published studies on human MNP subset distribution in blood, tonsils, BAL, and lung tissue to demonstrate the differential distribution of MNPs across anatomical compartments reported from many research groups ( 51 , 52 , 57 – 61 , 63 – 76 ). As different studies utilize different strategies to specifically define MNPs, the pie charts show groups of cells typically including several subsets of cells: Mϕs (beige), monocytes (green), myeloid DCs (MDCs) (coral), and plasmacytoid DCs (PDCs) (teal).…”

Section: Human Respiratory Mnpsmentioning

confidence: 99%

Respiratory Mononuclear Phagocytes in Human Influenza A Virus Infection: Their Role in Immune Protection and As Targets of the Virus

Vangeti

Smed‐Sörensen

2018

Front. Immunol.

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Emerging viruses have become increasingly important with recurrent epidemics. Influenza A virus (IAV), a respiratory virus displaying continuous re-emergence, contributes significantly to global morbidity and mortality, especially in young children, immunocompromised, and elderly people. IAV infection is typically confined to the airways and the virus replicates in respiratory epithelial cells but can also infect resident immune cells. Clearance of infection requires virus-specific adaptive immune responses that depend on early and efficient innate immune responses against IAV. Mononuclear phagocytes (MNPs), comprising monocytes, dendritic cells, and macrophages, have common but also unique features. In addition to being professional antigen-presenting cells, MNPs mediate leukocyte recruitment, sense and phagocytose pathogens, regulate inflammation, and shape immune responses. The immune protection mediated by MNPs can be compromised during IAV infection when the cells are also targeted by the virus, leading to impaired cytokine responses and altered interactions with other immune cells. Furthermore, it is becoming increasingly clear that immune cells differ depending on their anatomical location and that it is important to study them where they are expected to exert their function. Defining tissue-resident MNP distribution, phenotype, and function during acute and convalescent human IAV infection can offer valuable insights into understanding how MNPs maintain the fine balance required to protect against infections that the cells are themselves susceptible to. In this review, we delineate the role of MNPs in the human respiratory tract during IAV infection both in mediating immune protection and as targets of the virus.

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Human Lung Dendritic Cells: Spatial Distribution and Phenotypic Identification in Endobronchial Biopsies Using Immunohistochemistry and Flow Cytometry

Cited by 9 publications

References 22 publications

Human Lung Mononuclear Phagocytes in Health and Disease

Human Lung Mononuclear Phagocytes in Health and Disease

Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients

Respiratory Mononuclear Phagocytes in Human Influenza A Virus Infection: Their Role in Immune Protection and As Targets of the Virus

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