Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology
Interleukin-25 (IL-25) is a cytokine associated with allergy and asthma that functions to promote type 2 immune responses at mucosal epithelial surfaces and serves to protect against helminth parasitic infections in the intestinal tract. This study identifies the IL-25 receptor, IL-17RB, as a key mediator of both innate and adaptive pulmonary type 2 immune responses. Allergen exposure upregulated IL-25 and induced type 2 cytokine production in a previously undescribed granulocytic population, termed type 2 myeloid (T2M) cells. Il17rb(-/-) mice showed reduced lung pathology after chronic allergen exposure and decreased type 2 cytokine production in T2M cells and CD4(+) T lymphocytes. Airway instillation of IL-25 induced IL-4 and IL-13 production in T2M cells, demonstrating their importance in eliciting T cell-independent inflammation. The adoptive transfer of T2M cells reconstituted IL-25-mediated responses in Il17rb(-/-) mice. High-dose dexamethasone treatment did not reduce the IL-25-induced T2M pulmonary response. Finally, a similar IL-4- and IL-13-producing granulocytic population was identified in peripheral blood of human subjects with asthma. These data establish IL-25 and its receptor IL-17RB as targets for innate and adaptive immune responses in chronic allergic airway disease and identify T2M cells as a new steroid-resistant cell population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Nature medicine - 18(2012), 5 vom: 30. Mai, Seite 751-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Petersen, Bryan C [VerfasserIn] |
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| Links: |
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| Themen: |
7S5I7G3JQL |
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| Anmerkungen: |
Date Completed 27.07.2012 Date Revised 30.03.2022 published: Print GEO: GSE36392 Citation Status MEDLINE |
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| doi: |
10.1038/nm.2735 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM21738448X |
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| 100 | 1 | |a Petersen, Bryan C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Revised 30.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a GEO: GSE36392 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Interleukin-25 (IL-25) is a cytokine associated with allergy and asthma that functions to promote type 2 immune responses at mucosal epithelial surfaces and serves to protect against helminth parasitic infections in the intestinal tract. This study identifies the IL-25 receptor, IL-17RB, as a key mediator of both innate and adaptive pulmonary type 2 immune responses. Allergen exposure upregulated IL-25 and induced type 2 cytokine production in a previously undescribed granulocytic population, termed type 2 myeloid (T2M) cells. Il17rb(-/-) mice showed reduced lung pathology after chronic allergen exposure and decreased type 2 cytokine production in T2M cells and CD4(+) T lymphocytes. Airway instillation of IL-25 induced IL-4 and IL-13 production in T2M cells, demonstrating their importance in eliciting T cell-independent inflammation. The adoptive transfer of T2M cells reconstituted IL-25-mediated responses in Il17rb(-/-) mice. High-dose dexamethasone treatment did not reduce the IL-25-induced T2M pulmonary response. Finally, a similar IL-4- and IL-13-producing granulocytic population was identified in peripheral blood of human subjects with asthma. These data establish IL-25 and its receptor IL-17RB as targets for innate and adaptive immune responses in chronic allergic airway disease and identify T2M cells as a new steroid-resistant cell population | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Il17rb protein, mouse |2 NLM | |
| 650 | 7 | |a Interleukins |2 NLM | |
| 650 | 7 | |a Mydgf protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-17 |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 700 | 1 | |a Budelsky, Alison L |e verfasserin |4 aut | |
| 700 | 1 | |a Baptist, Alan P |e verfasserin |4 aut | |
| 700 | 1 | |a Schaller, Matthew A |e verfasserin |4 aut | |
| 700 | 1 | |a Lukacs, Nicholas W |e verfasserin |4 aut | |
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