TGF-beta and Immuno-evasion

Helmholtz-INSERM Unit TGF-beta and Immuno-evasion

Dr. Julien C. Marie

Picture of bone-joint illustrating the massive infiltration of lymphocytes in the absence of TGF- β control. (H&E staining X 80)
© dkfz.de

The immune system has to be ignorant against the self-cells to avoid autoimmunity, but in the same time it should also be able to eliminate the self-cells that are noxious for the organism such as tumor cells. Key actors of the tolerance should be ubiquitously expressed, highly abundant in immuno-privilege sites, present before T cell emigration from the thymus, and likely highly conserved between mammalians. Transforming Growth Factor beta (TGF-β) is the only actor fitting with all these criteria. The absence of this cytokine leads to massive autoimmunity touching all the organs. Interestingly, TGF-β is highly produced by the tumor microenvironment and contributes to tumor growth.
We revealed that within the immune system the target-cells of the regulatory effects of TGF-β are T lymphocytes and that TGF-β represses their activation against self-cells. More precisely using models with gain and loss of TGF-β signaling selectively in T cells, we demonstrated that TGF-β controls the pro-inflammatory and cytotoxic program of both CD4 and CD8 effector T cells, the length of T cell response and the early responses of memory cells. Moreover we revealed that TGF-β controls the homeostasis of different T cell subsets such as NKT cells, NK1.1 CD8 T cells, TFH cells and thymus derived Tregs. The Marie lab is one of the two Helmholtz-Inserm labs. It is localized in Lyon, France (4 hours travel from the Heidelberg) and is full part of the Tumor Immunology research program of the DKFZ.

The Marie lab is now investigating the cellular and molecular mechanisms by which TGF-β controls self-tolerance and their importance in the tumor-growth. The physiological approaches will involve careful analysis of the incriminated lymphocyte subsets, using loss and gain of function of TGF-β signaling through transgenic models. Our dynamic group developed key tools to understand the exiting role of TGF-β in tolerance and should propose several mechanisms for auto-immunity and tumor development.

Contact

Dr. Julien C. Marie
TGF-beta and Immuno-evasion ()

Cancer Research Center of Lyon C R C L
Dpt of Immunology, Virology and Inflammation
C R C L
Bat. Cheney A
28 rue Laennec
69 373 Lyon cedex 08
FRANCE

Tel: + 33 4 26 55 67 48/25
E-Mail: j.marie@dkfz.de

Selected Publications

  • McCarron MJ,and Marie JC.(2014) TGF-β prevents T follicular helper cell accumulation and B cell autoreactivity. J Clin Invest.124(10):4375-86.
  • Soudja SM, Ruiz AL, Marie JC, & Lauvau G (2012). Inflammatory monocytes activate memory CD8(+) T and innate NK Lymphocytes independent of cognate antigen during microbial pathogen Invasion. Immunity, 37, 549-562
  • Ruiz AL, Soudja SM, Deceneux C, Lauvau G, and Marie JC. (2014) NK1.1+ CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response. Nature Com. 6;5:5150.
  • Doisne JM, Bartholin L, Yan KP, Garcia CN, Duarte N, Le Luduec JB, Vincent D, Cyprian F, Horvat B, Martel S, Rimokh R, Losson R, Benlagha K, & Marie JC (2009). iNKT cell development is orchestrated by different branches of TGF-beta signaling.J. Exp. Med. 8,206, (6) 1365-1378
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