Cellular Stress Increases the Probability of Developing Autoimmune Diseases

send to a friend share this

Cellular Stress Increases the Probability of Developing Autoimmune Diseases

Tuesday, 01.08.2017

A team of researchers led by Marc Veldhoen, Instituto de Medicina Molecular (iMM), Lisboa, have found that cellular stress enhances the activation of certain type of immune cells implicated in many chronic inflammatory conditions, increasing the risk of autoimmune diseases. 

 

Authors and Affiliations:

Verena Brucklacher-Waldert 1, 8 Cristina Ferreira 1, 2, 8 Marisa Stebegg 1 Olivier Fesneau 3, 4, 5, 6 Silvia Innocentin 1 Julien C. Marie 3, 4, 5, 6, 7 Marc Veldhoen 1, 2, 9

1 Laboratory for Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK

2 Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular, Av. Professor Egas Moniz, Lisbon 1649-028, Portugal

3 Immunology Virology and Inflammation Department, Cancer Research Center of Lyon UMR INSERM1052, CNRS 5286 28 rue Laennec, Lyon 69373, Cedex 08, France

4 Université Lyon 1, Lyon 69000, France

5 Centre Léon Bérard, Lyon 69008, France

6 Labex DEVweCAN, Lyon 69008, France

7 TGFβ and Immuno-Evasion Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

 

Abstract:

T helper-17 (Th17) cells are associated with inflammatory disorders and cancer. We report that environmental conditions resulting in cellular stress, such as low oxygen, glucose, and isotonic stress, particularly enhance the generation of Th17 cells. Pharmacological inhibition of cell stress reduces Th17 cell differentiation while stress inducers enhance the development of Th17 cells. The cellular stress response results in Th17 cell development via sustained cytoplasmic calcium levels and, in part, XBP1 activity. Furthermore, in an inflammatory environment, conditions resulting in cell stress can bring about de novo Th17 cell differentiation, even in the absence of transforming growth factor β (TGF-β) signaling. In vivo, cell stress inhibition enhances resistance to Th17-mediated autoimmunity while stress-exposed T cells enhance disease severity. Adverse metabolic environments during inflammation provide a link between adaptive immunity and inflammation and may represent a risk factor for the development of chronic inflammatory conditions by facilitating Th17 cell differentiation.

 

Journal: Cell Reports

 

Linkhttp://www.sciencedirect.com/science/article/pii/S221112471730709X?via%3Dihub#!