Role of Fra2 in Treg development and autoimmunity

​Regulatory T cells (Tregs) form a particular subset of CD4+ T cells able to dampen inflammation and immunity. They are considered as an important mechanism of protection against autoimmune and chronic inflammatory diseases. Tregs have been shown to be reduced in function and/or numbers in a variety of different autoimmune diseases (1). Accordingly, they also represent promising targets for immunomodulatory therapies (2). Although important progress has been made in recent years in understanding the pathophysiology of Tregs, the pathways implicated in their development are still poorly described.

TREG.jpg

Causes of impaired TReg cell-mediated suppression in autoimmunity (1)

The AP1 transcription complex is a heterodimer of Jun and Fos family proteins. Fos related antigen 2 (Fra2) is a member of the Fos protein family and can form heterodimers with members of the Jun protein family. Fra2 has been shown to play a role in diverse biological processes, such as stress response, apoptosis or cell differentiation (3), and was implicated in the patho-mechanisms of the autoimmune disease systemic sclerosis (4,5). In T cells, very few data are available on the role of Fra2, but it has been proposed to control T cell plasticity by repressing Th17 differentiation (6).

The aim of this project is to understand the role of Fra2 in the control of Treg development and autoimmunity using in vitro and in vivo approaches. To this end, we recently generated, in collaboration with Sanofi-Genzyme, a new mouse strain, in which Fra2 is overexpressed under the control of the MHCI promotor H2Kb. These mice displayed a high expression of Fra2 in T cells, thus providing a valuable opportunity to study the function of this transcription factor in this cell type and in particular in the process of Treg differentiation.

References

  1. Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nature reviews Immunology. 2010;10(12):849-59.
  2. Singer BD, King LS, D'Alessio FR. Regulatory T cells as immunotherapy. Front Immunol. 2014;5:46.
  3. Hess J, Angel P, Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. J Cell Sci. 2004;117(Pt 25):5965-73.
  4. Maurer, B., J.H. Distler, and O. Distler, The Fra-2 transgenic mouse model of systemic sclerosis. Vascul Pharmacol, 2013. 58(3): p. 194-201.
  5. Maurer, B., et al., Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann Rheum Dis, 2012. 71(8): p. 1382-7.
  6. Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F, et al. A validated regulatory network for Th17 cell specification. Cell. 2012;151(2):289-303.

 


We use cookies to make our website user-friendly, to continuously improve it and to analyze the traffic of our website. By continuing to browse the site, you are agreeing to our use of cookies. Further information can be found in our privacy policy.