A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved..
BACKGROUND: Thymic stromal lymphopoietin (TSLP) controls allergic TH2 inflammatory responses through induction of distinct activation programs in dendritic cells (DCs). However, knowledge about TSLP receptor expression and functional consequences of receptor activation by DCs residing in the human respiratory tract is limited.
OBJECTIVE: We wanted to identify TSLP-responding DC populations in the human upper airway mucosa and assess the TSLP-mediated effects on such DCs in allergic airway responses.
RESULTS: We found that the TSLP receptor was constitutively and preferentially expressed by myeloid CD1c(+) DCs in the human airway mucosa and that the density of this DC subset in nasal mucosa increased significantly after in vivo allergen challenge of patients with allergic rhinitis. In vitro, TSLP strongly enhanced the capacity of CD1c(+) DCs to activate allergen-specific memory CD4(+) T cells. Moreover, TSLP rapidly induced CCR7 expression on CD1c(+) DCs. However, TH2 cytokines attenuated TSLP-mediated CCR7 induction, thus inhibiting the TSLP-induced DC migration potential to the draining lymph nodes.
CONCLUSION: Our results suggest that TSLP-mediated activation of human nasal mucosal CD1c(+) DCs triggers CCR7-dependent migration to the draining lymph nodes and enhances their capacity to initiate TH2 responses. However, the observation that TH2 cytokines abrogate the induction of CCR7 implies that during a TH2-mediated inflammatory reaction, TLSP-activated CD1c(+) DCs are retained in the inflamed tissue to further exacerbate local inflammation by activating local antigen-specific memory TH2 cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:134 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 134(2014), 3 vom: 14. Sept., Seite 613-621.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Melum, Guro R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.04.2015 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2014.05.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM239462815 |
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| 041 | |a eng | ||
| 100 | 1 | |a Melum, Guro R |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 16.04.2015 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved. | ||
| 520 | |a BACKGROUND: Thymic stromal lymphopoietin (TSLP) controls allergic TH2 inflammatory responses through induction of distinct activation programs in dendritic cells (DCs). However, knowledge about TSLP receptor expression and functional consequences of receptor activation by DCs residing in the human respiratory tract is limited | ||
| 520 | |a OBJECTIVE: We wanted to identify TSLP-responding DC populations in the human upper airway mucosa and assess the TSLP-mediated effects on such DCs in allergic airway responses | ||
| 520 | |a RESULTS: We found that the TSLP receptor was constitutively and preferentially expressed by myeloid CD1c(+) DCs in the human airway mucosa and that the density of this DC subset in nasal mucosa increased significantly after in vivo allergen challenge of patients with allergic rhinitis. In vitro, TSLP strongly enhanced the capacity of CD1c(+) DCs to activate allergen-specific memory CD4(+) T cells. Moreover, TSLP rapidly induced CCR7 expression on CD1c(+) DCs. However, TH2 cytokines attenuated TSLP-mediated CCR7 induction, thus inhibiting the TSLP-induced DC migration potential to the draining lymph nodes | ||
| 520 | |a CONCLUSION: Our results suggest that TSLP-mediated activation of human nasal mucosal CD1c(+) DCs triggers CCR7-dependent migration to the draining lymph nodes and enhances their capacity to initiate TH2 responses. However, the observation that TH2 cytokines abrogate the induction of CCR7 implies that during a TH2-mediated inflammatory reaction, TLSP-activated CD1c(+) DCs are retained in the inflamed tissue to further exacerbate local inflammation by activating local antigen-specific memory TH2 cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CCR7 | |
| 650 | 4 | |a Thymic stromal lymphopoietin | |
| 650 | 4 | |a airway allergy | |
| 650 | 4 | |a dendritic cells | |
| 650 | 4 | |a human airway mucosa | |
| 650 | 7 | |a Allergens |2 NLM | |
| 650 | 7 | |a Antigens, CD1 |2 NLM | |
| 650 | 7 | |a CCR7 protein, human |2 NLM | |
| 650 | 7 | |a CD1C protein, human |2 NLM | |
| 650 | 7 | |a CRLF2 protein, human |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Receptors, CCR7 |2 NLM | |
| 650 | 7 | |a Receptors, Cytokine |2 NLM | |
| 650 | 7 | |a Thymic Stromal Lymphopoietin |2 NLM | |
| 650 | 7 | |a GT0IL38SP4 |2 NLM | |
| 700 | 1 | |a Farkas, Lorant |e verfasserin |4 aut | |
| 700 | 1 | |a Scheel, Cecilie |e verfasserin |4 aut | |
| 700 | 1 | |a Van Dieren, Brenda |e verfasserin |4 aut | |
| 700 | 1 | |a Gran, Einar |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yong-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Johansen, Finn-Eirik |e verfasserin |4 aut | |
| 700 | 1 | |a Jahnsen, Frode L |e verfasserin |4 aut | |
| 700 | 1 | |a Baekkevold, Espen S |e verfasserin |4 aut | |
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