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IFN-α Production by...
IFN-α Production by Plasmacytoid Dendritic Cells Stimulated with RNA-Containing Immune Complexes Is Promoted by NK Cells via MIP-1β and LFA-1
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- Hagberg, Niklas (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Rheumatology, Systemic Autoimmmune Diseases
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- Berggren, Olof (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Rheumatology, Systemic Autoimmmune Diseases
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- Leonard, Dag (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Rheumatology, Systemic Autoimmmune Diseases
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Weber, Gert (author)
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- Bryceson, Yenan T. (author)
- Karolinska Institutet
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- Alm, Gunnar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health
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- Eloranta, Maija-Leena (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Rheumatology, Systemic Autoimmmune Diseases
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- Rönnblom, Lars (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Rheumatology, Systemic Autoimmmune Diseases
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(creator_code:org_t)
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- 2011-05-01
- 2011
- English.
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 186:9, s. 5085-5094
- Related links:
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http://www.jimmunol....
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https://urn.kb.se/re...
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https://doi.org/10.4...
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http://kipublication...
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https://res.slu.se/i...
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Abstract
Subject headings
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- Several systemic autoimmune diseases display a prominent IFN signature. This is caused by a continuous IFN-α production by plasmacytoid dendritic cells (pDCs), which are activated by immune complexes (ICs) containing nucleic acid. The IFN-α production by pDCs stimulated with RNA-containing IC (RNA-IC) consisting of anti-RNP autoantibodies and U1 small nuclear ribonucleoprotein particles was recently shown to be inhibited by monocytes, but enhanced by NK cells. The inhibitory effect of monocytes was mediated by TNF-α, PGE2, and reactive oxygen species, but the mechanisms for the NK cell-mediated increase in IFN-α production remained unclear. In this study, we investigated the mechanisms whereby NK cells increase the RNA-IC–induced IFN-α production by pDCs. Furthermore, NK cells from patients with systemic lupus erythematosus (SLE) were evaluated for their capacity to promote IFN-α production. We found that CD56dim NK cells could increase IFN-α production >1000-fold after RNA-IC activation, whereas CD56bright NK cells required costimulation by IL-12 and IL-18 to promote IFN-α production. NK cells produced MIP-1α, MIP-1β, RANTES, IFN-γ, and TNF-α via RNA-IC–mediated FcγRIIIA activation. The IFN-α production in pDCs was promoted by NK cells via MIP-1β secretion and LFA-mediated cell–cell contact. Moreover, NK cells from SLE patients displayed a reduced capacity to promote the RNA-IC–induced IFN-α production, which could be restored by exogenous IL-12 and IL-18. Thus, different molecular mechanisms can mediate the NK cell-dependent increase in IFN-α production by RNA-IC–stimulated pDCs, and our study suggests that the possibility to therapeutically target the NK–pDC axis in IFN-α–driven autoimmune diseases such as SLE should be investigated.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- interferon
- plasmacytoid dendritic cells
- MIP-1beta
- NK cells
- MEDICINE
- MEDICIN
- Rheumatology
- Reumatologi
- Medicin
- Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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