Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Tolerogenic Dendritic Cells from Poorly Compensated Type 1 Diabetes Patients Have Decreased Ability To Induce Stable Antigen-Specific T Cell Hyporesponsiveness and Generation of Suppressive Regulatory T Cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Multiple Homozygous Variants in the STING-Encoding TMEM173 Gene in HIV Long-Term Nonprogressors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Changes in Gene Expression during G-CSF-Induced Emergency Granulopoiesis in Humans

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Possible Prevention of Diabetes with a Gluten-Free Diet

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Oral insulin does not alter gut microbiota composition of NOD mice

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Abnormal islet sphingolipid metabolism in type 1 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Klára Dáňová
  • Anna Grohová
  • Pavla Strnadová
  • David P Funda
  • Zdeněk Šumník
  • Jan Lebl
  • Ondřej Cinek
  • Štěpánka Průhová
  • Stanislava Koloušková
  • Barbora Obermannová
  • Lenka Petruželková
  • Anna Šedivá
  • Petra Fundová
  • Karsten Buschard
  • Radek Špíšek
  • Lenka Palová-Jelínková
Vis graf over relationer

Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients. tolDCs differentiated from both groups of patients acquired a regulatory phenotype and an anti-inflammatory profile. Interestingly, tolDCs from well-controlled patients expressed higher levels of inhibitory molecules IL-T3 and PD-L1. Additionally, glutamic acid decarboxylase (GAD)65-loaded tolDCs from well-controlled patients decreased significantly primary Th1/Th17 responses, induced stable GAD65-specific T cell hyporesponsiveness, and suppressed markedly control DC-induced GAD65-specific T cell activation compared with poorly controlled patients. The ability of tolDCs from poorly controlled patients to induce durable GAD65-specific T cell hyporesponsiveness was reversed once the control of glycemia improved. In both groups of patients, tolDCs were able to induce regulatory T cells from autologous naive CD4(+) T cells. However, regulatory T cells from well-controlled patients had better suppressive abilities. The functionality of tolDCs was confirmed in the adoptive transfer model of NOD-SCID mice where tolDCs delayed diabetes onset. These results suggest that metabolic control of T1D affects the functional characteristics of tolDCs and subsequent effector T cell responses. Metabolic control may be relevant for refining inclusion criteria of clinical trials in the settings of T1D.

OriginalsprogEngelsk
TidsskriftJournal of immunology (Baltimore, Md. : 1950)
Vol/bind198
Udgave nummer2
Sider (fra-til)729-740
Antal sider12
ISSN0022-1767
DOI
StatusUdgivet - 15 jan. 2017

ID: 49819702