miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

Scherm MG, Serr I, Zahm AM, Schug J, Bellusci S, Manfredini R, Salb VK, Gerlach K, Weigmann B, Ziegler AG, Kaestner KH, Daniel C (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 10

Article Number: 5697

Journal Issue: 1

DOI: 10.1038/s41467-019-13587-3

Abstract

In type 1 diabetes, the appearance of islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in the destruction of pancreatic beta cells, molecular underpinnings promoting aberrant T cell activation remain poorly understood. Here, we show that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity and that its inhibition enhances Treg induction and stability, leading to reduced islet autoimmunity in non-obese diabetic mice. Using various cellular and molecular approaches we identify Tet2 as a direct target of miR142-3p, thereby linking high miR142-3p levels to epigenetic remodeling in Tregs. These findings offer a mechanistic model where during islet autoimmunity miR142-3p/Tet2-mediated Treg instability contributes to autoimmune activation and progression.

Authors with CRIS profile

Katharina Gerlach Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Medizinische Fakultät

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich

Germany (DE) University of Pennsylvania

United States (USA) (US) Justus-Liebig-Universität Gießen

Germany (DE) Università degli Studi di Modena e Reggio Emilia (UNIMORE)

Italy (IT)

How to cite

APA:

Scherm, M.G., Serr, I., Zahm, A.M., Schug, J., Bellusci, S., Manfredini, R.,... Daniel, C. (2019). miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-13587-3

MLA:

Scherm, Martin G., et al. "miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes." Nature Communications 10.1 (2019).

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