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Vitamin D downregul...
Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells
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- Konya, Viktoria (författare)
- Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Czarnewski, Paulo (författare)
- Sci Life Lab, Sweden
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- Forkel, Marianne (författare)
- Karolinska Inst, Sweden
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- Rao, Anna (författare)
- Karolinska Inst, Sweden
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- Kokkinou, Efthymia (författare)
- Karolinska Inst, Sweden
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- Villablanca, Eduardo J. (författare)
- Karolinska Institutet,Sci Life Lab, Sweden
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- Almer, Sven (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden
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- Lindforss, Ulrik (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden
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- Friberg, Danielle (författare)
- Uppsala universitet,Karolinska Institutet,Karolinska Univ Hosp, Sweden,Öron-, näs- och halssjukdomar
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- Hoeoeg, Charlotte (författare)
- Karolinska Univ Hosp, Sweden
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- Bergman, Peter (författare)
- Karolinska Institutet,Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Mjösberg, Jenny (författare)
- Karolinska Institutet,Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Karolinska Inst, Sweden
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- Hoog, C (författare)
- Karolinska Institutet
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(creator_code:org_t)
- MOSBY-ELSEVIER, 2018
- 2018
- Engelska.
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 141:1, s. 279-292
- Relaterad länk:
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http://www.jacionlin...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Background: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident group 3 innate lymphoid cells (ILC3s) play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy. Objective: We set out to define the role of 1 alpha,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3s to IL-23 plus Il-1 beta stimulation. Methods: Transcriptomes of sorted tonsillar ILC3s were assessed by using microarray analysis. ILC3 cytokine production, proliferation, and differentiation were determined by means of flow cytometry, ELISA, and multiplex immunoassay. Intestinal cell suspensions and ILC3s sorted from gut biopsy specimens of patients with IBD were also analyzed along with plasma 25-hydroxy vitamin D3 (25D) detection. Results: ILC3s stimulated with IL-23 plus IL-1 beta upregulated the vitamin D receptor and responded to 1,25D with downregulation of the IL-23 receptor pathway. Consequently, 1,25D suppressed IL-22, IL-17F, and GM-CSF production from tonsillar and gut ILC3s. In parallel, 1,25D upregulated genes linked to the IL-1 beta signaling pathway, as well as the IL-1 beta-inducible cytokines IL-6, IL-8, and macrophage inflammatory protein IL/1 beta. The 1,25D-triggered skewing in ILC3 function was not accompanied or caused by changes in viability, proliferation, or phenotype. Finally, we confirmed low 25D plasma levels in patients with IBD with active inflammation. Conclusion: In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.
Ämnesord
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Oto-rhino-laryngologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Otorhinolaryngology (hsv//eng)
Nyckelord
- Innate lymphoid cells; inflammatory bowel diseases; vitamin D receptor; IL-22
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Konya, Viktoria
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Czarnewski, Paul ...
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Forkel, Marianne
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Rao, Anna
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Kokkinou, Efthym ...
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Villablanca, Edu ...
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visa fler...
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Almer, Sven
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Lindforss, Ulrik
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Friberg, Daniell ...
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Hoeoeg, Charlott ...
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Bergman, Peter
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Mjösberg, Jenny
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Hoog, C
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Immunologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Oto rhino laryng ...
- Artiklar i publikationen
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Journal of Aller ...
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet
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Uppsala universitet