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  • Wasén, CarolineGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research (author)

Smoking activates cytotoxic CD8(+) T cells and causes survivin release in rheumatoid arthritis

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • Elsevier BV,2017
  • electronicrdacarrier

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  • LIBRIS-ID:oai:gup.ub.gu.se/253303
  • https://gup.ub.gu.se/publication/253303URI
  • https://doi.org/10.1016/j.jaut.2016.12.009DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135502350URI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • CD8(+) T cells have an emerging role in RA. Resent research indicates a causal relationship between the non-exhausted state of CD8(+) T cells, defined by lost function of PD-1, and development of arthritis. We investigated how smoking contributes to the non-exhausted phenotype of CD8(+) T cells and cause survivin release to serum. We compared serum survivin levels between smokers and non-smokers in 252 RA and 168 healthy subjects. Nicotine effects on CD8(+) T cells were studied in peripheral blood of smoking women, bone marrow of nicotine treated mice and in sorted CD8 spleen cells in vitro using flow cytometry and quantitative PCR. Smoking increased the frequency of survivin release in serum of healthy women (OR 3.64, p = 0.025) and in RA patients (OR 1.98, p = 0.039). CD8(+) T cells of smokers gained a non-exhausted PD-1 deficient phenotype. Expression of the cytotoxic marker CD107 correlated to survivin levels in serum. In the experimental setting, nicotine exposure led to an accumulation of non-exhausted PD-1(-)IL-7R(+) CD8(+) T cells in the bone marrow that is abundant with survivin producing cells. The production of the cytolytic protein perforin in bone marrow correlated to serum survivin levels. In vitro stimulation of nicotinic receptors on murine CD8+ T cells induced repressive transcription factors T-bet and Blimp-1 in support of the non-exhausted phenotype. We conclude that nicotine contributes to autoimmunity by supporting the non-exhausted state of CD8+ T cells resulting in the release of survivin. This presents a new mechanism by which smoking may contribute to the pathogenesis of RA. (C) 2016 The Authors. Published by Elsevier Ltd.

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  • Turkkila, MinnaGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research (author)
  • Bossios, Apostolos,1969Gothenburg University,Göteborgs universitet,Krefting Research Centre,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xbosap (author)
  • Erlandsson, Malin,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xerlma (author)
  • Andersson, Karin,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xankar (author)
  • Ekerljung, Linda,1979Gothenburg University,Göteborgs universitet,Krefting Research Centre,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xekeli (author)
  • Malmhäll, Carina,1959Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Krefting Research Centre,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmalmc (author)
  • Brisslert, Mikael,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xbrimi (author)
  • Silfverswärd Lindblad, Sofia,1980Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xsilso (author)
  • Lundbäck, Bo,1948Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Krefting Research Centre,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlunbo (author)
  • Bokarewa, Maria,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xbokma (author)
  • Silfversward, ST (author)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning (creator_code:org_t)

Related titles

  • In:Journal of Autoimmunity: Elsevier BV78, s. 101-1100896-84111095-9157

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