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Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling

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Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling. / Shalaby, Karim H; Lyons-Cohen, Miranda R; Whitehead, Gregory S; Thomas, Seddon Y; Prinz, Immo; Nakano, Hideki; Cook, Donald N.

In: J ALLERGY CLIN IMMUN, Vol. 142, No. 4, 10.2018, p. 1229-1242.e6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Shalaby, KH, Lyons-Cohen, MR, Whitehead, GS, Thomas, SY, Prinz, I, Nakano, H & Cook, DN 2018, 'Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling', J ALLERGY CLIN IMMUN, vol. 142, no. 4, pp. 1229-1242.e6. https://doi.org/10.1016/j.jaci.2017.10.023

APA

Shalaby, K. H., Lyons-Cohen, M. R., Whitehead, G. S., Thomas, S. Y., Prinz, I., Nakano, H., & Cook, D. N. (2018). Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling. J ALLERGY CLIN IMMUN, 142(4), 1229-1242.e6. https://doi.org/10.1016/j.jaci.2017.10.023

Vancouver

Shalaby KH, Lyons-Cohen MR, Whitehead GS, Thomas SY, Prinz I, Nakano H et al. Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling. J ALLERGY CLIN IMMUN. 2018 Oct;142(4):1229-1242.e6. https://doi.org/10.1016/j.jaci.2017.10.023

Bibtex

@article{30c6bfaf31d44c6b912595ab344f96ae,
title = "Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling",
abstract = "BACKGROUND: Mechanisms that elicit mucosal TH17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear.OBJECTIVE: We sought to understand whether maintenance of lung TH17 inflammation requires environmental agents in addition to antigen and to identify the lung antigen-presenting cell (APC) types that sustain the self-renewal of TH17 cells.METHODS: Animals were exposed repeatedly to aspiration of ovalbumin alone or together with environmental adjuvants, including common house dust extract (HDE), to test their role in maintaining lung inflammation. Alternatively, antigen-specific effector/memory TH17 cells, generated in culture with CD4+ T cells from Il17a fate-mapping mice, were adoptively transferred to assess their persistence in genetically modified animals lacking distinct lung APC subsets or cell-specific Toll-like receptor (TLR) 4 signaling. TH17 cells were also cocultured with lung APC subsets to determine which of these could revive their expansion and activation.RESULTS: TH17 cells and the consequent neutrophilic inflammation were poorly sustained by inhaled antigen alone but were augmented by inhalation of antigen together with HDE. This was associated with weight loss and changes in lung physiology consistent with interstitial lung disease. The effect of HDE required TLR4 signaling predominantly in lung hematopoietic cells, including CD11c+ cells. CD103+ and CD11b+ conventional dendritic cells interacted directly with TH17 cells in situ and revived the clonal expansion of TH17 cells both ex vivo and in vivo, whereas lung macrophages and B cells could not.CONCLUSION: TH17-dependent inflammation in the lungs can be sustained by persistent TLR4-mediated activation of lung conventional dendritic cells.",
keywords = "Allergens/immunology, Animals, Aspergillus oryzae/immunology, Dendritic Cells/immunology, Dust, Endotoxins/immunology, Inflammation/immunology, Lung/immunology, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin/immunology, Th17 Cells/immunology, Toll-Like Receptor 4/genetics",
author = "Shalaby, {Karim H} and Lyons-Cohen, {Miranda R} and Whitehead, {Gregory S} and Thomas, {Seddon Y} and Immo Prinz and Hideki Nakano and Cook, {Donald N}",
note = "Published by Elsevier Inc.",
year = "2018",
month = oct,
doi = "10.1016/j.jaci.2017.10.023",
language = "English",
volume = "142",
pages = "1229--1242.e6",
journal = "J ALLERGY CLIN IMMUN",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Pathogenic TH17 inflammation is sustained in the lungs by conventional dendritic cells and Toll-like receptor 4 signaling

AU - Shalaby, Karim H

AU - Lyons-Cohen, Miranda R

AU - Whitehead, Gregory S

AU - Thomas, Seddon Y

AU - Prinz, Immo

AU - Nakano, Hideki

AU - Cook, Donald N

N1 - Published by Elsevier Inc.

PY - 2018/10

Y1 - 2018/10

N2 - BACKGROUND: Mechanisms that elicit mucosal TH17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear.OBJECTIVE: We sought to understand whether maintenance of lung TH17 inflammation requires environmental agents in addition to antigen and to identify the lung antigen-presenting cell (APC) types that sustain the self-renewal of TH17 cells.METHODS: Animals were exposed repeatedly to aspiration of ovalbumin alone or together with environmental adjuvants, including common house dust extract (HDE), to test their role in maintaining lung inflammation. Alternatively, antigen-specific effector/memory TH17 cells, generated in culture with CD4+ T cells from Il17a fate-mapping mice, were adoptively transferred to assess their persistence in genetically modified animals lacking distinct lung APC subsets or cell-specific Toll-like receptor (TLR) 4 signaling. TH17 cells were also cocultured with lung APC subsets to determine which of these could revive their expansion and activation.RESULTS: TH17 cells and the consequent neutrophilic inflammation were poorly sustained by inhaled antigen alone but were augmented by inhalation of antigen together with HDE. This was associated with weight loss and changes in lung physiology consistent with interstitial lung disease. The effect of HDE required TLR4 signaling predominantly in lung hematopoietic cells, including CD11c+ cells. CD103+ and CD11b+ conventional dendritic cells interacted directly with TH17 cells in situ and revived the clonal expansion of TH17 cells both ex vivo and in vivo, whereas lung macrophages and B cells could not.CONCLUSION: TH17-dependent inflammation in the lungs can be sustained by persistent TLR4-mediated activation of lung conventional dendritic cells.

AB - BACKGROUND: Mechanisms that elicit mucosal TH17 cell responses have been described, yet how these cells are sustained in chronically inflamed tissues remains unclear.OBJECTIVE: We sought to understand whether maintenance of lung TH17 inflammation requires environmental agents in addition to antigen and to identify the lung antigen-presenting cell (APC) types that sustain the self-renewal of TH17 cells.METHODS: Animals were exposed repeatedly to aspiration of ovalbumin alone or together with environmental adjuvants, including common house dust extract (HDE), to test their role in maintaining lung inflammation. Alternatively, antigen-specific effector/memory TH17 cells, generated in culture with CD4+ T cells from Il17a fate-mapping mice, were adoptively transferred to assess their persistence in genetically modified animals lacking distinct lung APC subsets or cell-specific Toll-like receptor (TLR) 4 signaling. TH17 cells were also cocultured with lung APC subsets to determine which of these could revive their expansion and activation.RESULTS: TH17 cells and the consequent neutrophilic inflammation were poorly sustained by inhaled antigen alone but were augmented by inhalation of antigen together with HDE. This was associated with weight loss and changes in lung physiology consistent with interstitial lung disease. The effect of HDE required TLR4 signaling predominantly in lung hematopoietic cells, including CD11c+ cells. CD103+ and CD11b+ conventional dendritic cells interacted directly with TH17 cells in situ and revived the clonal expansion of TH17 cells both ex vivo and in vivo, whereas lung macrophages and B cells could not.CONCLUSION: TH17-dependent inflammation in the lungs can be sustained by persistent TLR4-mediated activation of lung conventional dendritic cells.

KW - Allergens/immunology

KW - Animals

KW - Aspergillus oryzae/immunology

KW - Dendritic Cells/immunology

KW - Dust

KW - Endotoxins/immunology

KW - Inflammation/immunology

KW - Lung/immunology

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Ovalbumin/immunology

KW - Th17 Cells/immunology

KW - Toll-Like Receptor 4/genetics

U2 - 10.1016/j.jaci.2017.10.023

DO - 10.1016/j.jaci.2017.10.023

M3 - SCORING: Journal article

C2 - 29154958

VL - 142

SP - 1229-1242.e6

JO - J ALLERGY CLIN IMMUN

JF - J ALLERGY CLIN IMMUN

SN - 0091-6749

IS - 4

ER -