βig-h3 represses T-cell activation in type 1 diabetes

Maeva Patry, Romain Teinturier, Delphine Goehrig, Cornelia Zetu, Doriane Ripoche, In-San Kim, Philippe Bertolino, Ana Hennino

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

βig-h3/TGF-βi is a secreted protein capable of binding to both extracellular matrix and cells. Human genetic studies recently revealed that in the tgfbi gene encoding for βig-h3, three single nucleotide polymorphisms were significantly associated with type 1 diabetes (T1D) risk. Pancreatic islets express βig-h3 in physiological conditions, but this expression is reduced in b-cell insult in T1D. Since the integrity of islets is destroyed by autoimmune T lymphocytes, we thought to investigate the impact of βig-h3 on T-cell activation. We show here that βig-h3 inhibits T-cell activation markers as well as cytotoxic molecule production as granzyme B and IFN-γ. Furthermore, βig-h3 inhibits early T-cell receptor signaling by repressing the activation of the early kinase protein Lck. Moreover, βig-h3-treated T cells are unable to induce T1D upon transfer in Rag2 knockout mice. Our study demonstrates for the first time that T-cell activation is modulated by βig-h3, an islet extracellular protein, in order to efficiently avoid autoimmune response.

Original languageEnglish
Pages (from-to)4212-4219
Number of pages8
JournalDiabetes
Volume64
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

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Type 1 Diabetes Mellitus
T-Lymphocytes
Granzymes
Immunoglobulin Genes
Medical Genetics
T-Cell Antigen Receptor
Autoimmunity
Islets of Langerhans
Protein Binding
Knockout Mice
Protein Kinases
Single Nucleotide Polymorphism
Extracellular Matrix
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Patry, M., Teinturier, R., Goehrig, D., Zetu, C., Ripoche, D., Kim, I-S., ... Hennino, A. (2015). βig-h3 represses T-cell activation in type 1 diabetes. Diabetes, 64(12), 4212-4219. https://doi.org/10.2337/db15-0638

βig-h3 represses T-cell activation in type 1 diabetes. / Patry, Maeva; Teinturier, Romain; Goehrig, Delphine; Zetu, Cornelia; Ripoche, Doriane; Kim, In-San; Bertolino, Philippe; Hennino, Ana.

In: Diabetes, Vol. 64, No. 12, 01.12.2015, p. 4212-4219.

Research output: Contribution to journalArticle

Patry, M, Teinturier, R, Goehrig, D, Zetu, C, Ripoche, D, Kim, I-S, Bertolino, P & Hennino, A 2015, 'βig-h3 represses T-cell activation in type 1 diabetes', Diabetes, vol. 64, no. 12, pp. 4212-4219. https://doi.org/10.2337/db15-0638
Patry M, Teinturier R, Goehrig D, Zetu C, Ripoche D, Kim I-S et al. βig-h3 represses T-cell activation in type 1 diabetes. Diabetes. 2015 Dec 1;64(12):4212-4219. https://doi.org/10.2337/db15-0638
Patry, Maeva ; Teinturier, Romain ; Goehrig, Delphine ; Zetu, Cornelia ; Ripoche, Doriane ; Kim, In-San ; Bertolino, Philippe ; Hennino, Ana. / βig-h3 represses T-cell activation in type 1 diabetes. In: Diabetes. 2015 ; Vol. 64, No. 12. pp. 4212-4219.
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