T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta - PubMed (original) (raw)
. 2009 May;65(5):499-509.
doi: 10.1002/ana.21652.
Affiliations
- PMID: 19475668
- DOI: 10.1002/ana.21652
T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta
Luca Durelli et al. Ann Neurol. 2009 May.
Abstract
Objective: T-helper 1 (Th1) and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression sensitivity to IFN-beta in MS patients.
Methods: In 30 untreated patients with active MS (AMS) and 32 with inactive MS (IMS), and in 22 healthy subjects, we measured intracellular cytokine expression, interleukin-17-producing myelin basic protein-stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-alphaR1) expression, IFN-beta-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation, and apoptosis of anti-CD3 monoclonal antibody-stimulated PB lymphocytes.
Results: Th17 cell percentage increased around sevenfold in AMS compared with IMS or healthy subjects, but there was no change in Th1 cells. Th17 cells in AMS were myelin basic protein specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-alphaR1 expression, IFN-beta-induced STAT1 activation, and apoptosis were significantly greater in Th17 than Th1 cells. IFN-alphaR1 expression and IFN-beta-dependent STAT1 activation progressively increased in vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells.
Interpretation: Evidence that an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, is associated with disease activity in MS. The greater IFN-alphaR1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-beta therapy.
Comment in
- New pieces in the puzzle: how does interferon-beta really work in multiple sclerosis?
Mitsdoerffer M, Kuchroo V. Mitsdoerffer M, et al. Ann Neurol. 2009 May;65(5):487-8. doi: 10.1002/ana.21722. Ann Neurol. 2009. PMID: 19479722 No abstract available.
Similar articles
- IFN-beta inhibits human Th17 cell differentiation.
Ramgolam VS, Sha Y, Jin J, Zhang X, Markovic-Plese S. Ramgolam VS, et al. J Immunol. 2009 Oct 15;183(8):5418-27. doi: 10.4049/jimmunol.0803227. Epub 2009 Sep 25. J Immunol. 2009. PMID: 19783688 - Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells.
Guo Z, Zheng C, Chen Z, Gu D, Du W, Ge J, Han Z, Yang R. Guo Z, et al. Eur J Immunol. 2009 Oct;39(10):2840-9. doi: 10.1002/eji.200839070. Eur J Immunol. 2009. PMID: 19637224 - Differentiation imbalance of Th1/Th17 in peripheral blood mononuclear cells might contribute to pathogenesis of Hashimoto's thyroiditis.
Shi Y, Wang H, Su Z, Chen J, Xue Y, Wang S, Xue Y, He Z, Yang H, Zhou C, Kong F, Liu Y, Yang P, Lu L, Shao Q, Huang X, Xu H. Shi Y, et al. Scand J Immunol. 2010 Sep;72(3):250-5. doi: 10.1111/j.1365-3083.2010.02425.x. Scand J Immunol. 2010. PMID: 20696023 - Properties and origin of human Th17 cells.
Romagnani S, Maggi E, Liotta F, Cosmi L, Annunziato F. Romagnani S, et al. Mol Immunol. 2009 Nov;47(1):3-7. doi: 10.1016/j.molimm.2008.12.019. Epub 2009 Feb 3. Mol Immunol. 2009. PMID: 19193443 Review. - Interferon-beta: mechanism of action and dosing issues.
Markowitz CE. Markowitz CE. Neurology. 2007 Jun 12;68(24 Suppl 4):S8-11. doi: 10.1212/01.wnl.0000277703.74115.d2. Neurology. 2007. PMID: 17562848 Review.
Cited by
- Multiple Sclerosis and Autoimmunity: A Veiled Relationship.
Barkhane Z, Elmadi J, Satish Kumar L, Pugalenthi LS, Ahmad M, Reddy S. Barkhane Z, et al. Cureus. 2022 Apr 19;14(4):e24294. doi: 10.7759/cureus.24294. eCollection 2022 Apr. Cureus. 2022. PMID: 35607574 Free PMC article. Review. - Do Th17 Lymphocytes and IL-17 Contribute to Parkinson's Disease? A Systematic Review of Available Evidence.
Storelli E, Cassina N, Rasini E, Marino F, Cosentino M. Storelli E, et al. Front Neurol. 2019 Jan 24;10:13. doi: 10.3389/fneur.2019.00013. eCollection 2019. Front Neurol. 2019. PMID: 30733703 Free PMC article. Review. - S-nitrosoglutathione reductase (GSNOR) inhibitor as an immune modulator in experimental autoimmune encephalomyelitis.
Saxena N, Won J, Choi S, Singh AK, Singh I. Saxena N, et al. Free Radic Biol Med. 2018 Jun;121:57-68. doi: 10.1016/j.freeradbiomed.2018.04.558. Epub 2018 Apr 22. Free Radic Biol Med. 2018. PMID: 29694854 Free PMC article. - Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation.
Mazzola MA, Raheja R, Murugaiyan G, Rajabi H, Kumar D, Pertel T, Regev K, Griffin R, Aly L, Kivisakk P, Nejad P, Patel B, Gwanyalla N, Hei H, Glanz B, Chitnis T, Weiner HL, Gandhi R. Mazzola MA, et al. J Neuroinflammation. 2015 Dec 30;12:245. doi: 10.1186/s12974-015-0460-z. J Neuroinflammation. 2015. PMID: 26714756 Free PMC article. - CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells.
Restorick SM, Durant L, Kalra S, Hassan-Smith G, Rathbone E, Douglas MR, Curnow SJ. Restorick SM, et al. Brain Behav Immun. 2017 Aug;64:71-79. doi: 10.1016/j.bbi.2017.03.008. Epub 2017 Mar 20. Brain Behav Immun. 2017. PMID: 28336414 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous