Mononuclear Cells in Human Lung Parenchyma: Characterization of a Potent Accessory Cell Not Obtained by Bronchoalveolar Lavage

Nicod, Laurent P.; Lipscomb, Mary F.; Weissler, Jonathan C.; Lyons, C. Rick; Albertson, John N.; Toews, Galen B.

doi:10.1164/ajrccm/136.4.818

Cited by 75 publications

(22 citation statements)

References 15 publications

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“…We viewed this as an important step in our studies for various reasons. First, alveolar macrophages have been shown to inhibit the Ag-presenting function of DCs (37,38). Second, in addition to CD11c, DCs and macrophages can share other markers as well, including those previously thought to be lineage specific (34,39).…”

Section: Phenotype Of Lung Draining Lymph Node Dcs Under Tolerogenic mentioning

confidence: 99%

Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance

Oriss

Ostroukhova

Seguin-Devaux

et al. 2005

The Journal of Immunology

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An emerging concept is that different types of dendritic cells (DCs) initiate different immune outcomes, such as tolerance vs inflammation. In this study, we have characterized the DCs from the lung draining lymph nodes of mice immunized for allergic airway inflammation or tolerance and examined their interactions with CD4+ T cells. The DC population derived from tolerized mice was predominantly CD11c+, B220+, Gr-1+, CD11b−, and MHC class IIlow, which resembled plasmacytoid-type DCs whereas DCs from the inflammatory condition were largely CD11c+, B220−, Gr-1−, CD11b+, and MHC class IIhigh resembling myeloid-type DCs. The DCs from the tolerogenic condition were poor inducers of T cell proliferation. DCs from both conditions induced T cell IL-4 production but the T cells cultured with tolerogenic DCs were unresponsive to IL-4 as indicated by inhibition of STAT6 activation and expression of growth factor-independent 1, which has been recently shown to be important for STAT6-activated Th2 cell expansion. Our data suggest that airway tolerance vs inflammation is determined by the DC phenotype in lung draining lymph nodes.

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Section: Phenotype Of Lung Draining Lymph Node Dcs Under Tolerogenic mentioning

confidence: 99%

Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance

Oriss

Ostroukhova

Seguin-Devaux

et al. 2005

The Journal of Immunology

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“…Research since the late 1980s has shown an important role for DCs in pulmonary immune responses (3,(5)(6)(7)(8)(9)(10)(11)(12)(13). DCs are present in high density in the proximal airways and are well positioned to capture Ags.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide

Chen

Arora

Yarlagadda

et al. 2006

The Journal of Immunology

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Dendritic cells (DCs) sense various components of invading pathogens via pattern recognition receptors such as TLRs. CpG oligodeoxynucleotides (ODNs), which mimic bacterial DNA, inhibit allergic airways disease and promote responses in the spleen to bacterial components. Because many TLR agonists are currently being tested for potential therapeutic effects, it is important to characterize the expression and function of TLRs in different tissues. We show that both myeloid and plasmacytoid DCs in the spleen express TLR9, the receptor for CpG ODNs, but lung DCs show no detectable expression in either subset. TLR4 expression in contrast was detected on both lung and spleen DCs. LPS was superior to CpG ODN in increasing the allostimulatory potential of lung DCs and their expression of CD40. However, both agonists efficiently stimulated spleen DCs. CpG ODNs administered to mice efficiently inhibited Th2 cytokine production both in the lung draining lymph node and in the spleen. Surprisingly, inhibition of Th2 cytokine production was evident despite high levels of expression of GATA-3 and additional transcription factors that regulate Th2 responses. Although in the spleen CpG ODNs induced IL-6, a key cytokine induced via TLR9-MyD88 signaling, no IL-6 was detectable in lung LN cells. These studies show for the first time that lung DCs lack TLR9 expression, but, despite this deficiency, CpG ODNs induce potent inhibitory effects on Th2 cytokine production in the lung without inducing expression of the proinflammatory cytokine, IL-6, which has been linked to chronic diseases in the lung and the gut.

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“…In this regard, previous studies have demonstrated that LC/DC isolated from the lung of humans and several animal species are potent accessory cells (7,8,(10)(11)(12)(13)(14), and differences in the functional activity ofcells present in airways and within the lung interstitium have recently been described (41 ).…”

Section: Further Characterization Ofdc/lc In Lung Carcinomasmentioning

confidence: 99%

“…Both LC and DC are present in human lung (7)(8)(9) and several studies have suggested that these cells, which are considerably better accessory cells than alveolar macrophages (8,10,11 ), could be involved in the immune defense of this organ (7,8,(10)(11)(12)(13)(14). LC have been also identi-fied infiltrating a variety of cancers, including lung cancers (15)(16)(17)(18) and a potential role for DC/LC in antitumoral immunity has also been suggested ( 19,20).…”

Section: Introductionmentioning

confidence: 99%

Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.

Tazi

Bouchonnet²,

Grandsaigne³

et al. 1993

J. Clin. Invest.

190

101

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GM-CSF has been shown to be important for the survival and function of cells of dendritic cell/Langerhans cell (LC) lineage in vitro. Since these cells have been demonstrated to infiltrate human lung and some lung carcinomas, we hypothesized that the production of GM-CSF in the lung could be important in their recruitment and differentiation. Using both immunohistochemistry and in situ hybridization, we have shown that: (a) GM-CSF was produced by normal bronchiolar epithelium, the only site were CD1a+ LC are observed in the normal lung, whereas neither GM-CSF production nor LC were identified in normal alveolar epithelium. (b) In inflamed pulmonary tissue, hyperplastic alveolar cells produced GM-CSF, and CDla+ LC accumulated adjacent to these cells. (c) Some, but not all, lung carcinomas produced this cytokine, and a close correlation was found between the production of GM-CSF and the number of CDla+ LC infiltrating these tumors. Since GM-CSF was produced at all sites where CDla+ LC are known to accumulate, but not at other locations within the lung, these data suggest that the local production of GM-CSF by certain lung cells may play an important role in determining the distribution and differentiated state of dendritic cell/LC in the human lung. (J. Clin. Invest. 1993. 91:566-576.)

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Mononuclear Cells in Human Lung Parenchyma: Characterization of a Potent Accessory Cell Not Obtained by Bronchoalveolar Lavage

Cited by 75 publications

References 15 publications

Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance

Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance

Distinct Responses of Lung and Spleen Dendritic Cells to the TLR9 Agonist CpG Oligodeoxynucleotide

Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.

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