The role of the adaptive immune system in autoimmunity: the breakdown of self-tolerance
Immunobiology of tolerogenic DC and Treg cells
Antigen presenting cells (APCs), especially dendritic cells (DCs), play a major role in the hierarchy of the induction of immune reactions. DCs are widely accepted as the most potent APCs capable of inducing protective adaptive immune responses in addition to tolerance to self-antigens. The role of DCs is currently being investigated in the context of many disease and therapeutic settings. In response to a variety of danger stimuli, resting DCs in peripheral tissues undergo a complex maturation process that might involve the regulation of genes that control distinct DC functions. The different functional properties of DCs are also linked to the existence of several subpopulations in humans and animals that differ in response to stimuli. On the other hand, immune reactions can be controlled by the so-called regulatory T cells that can interact with APCs such as DCs. Two main types of regulatory T cells have been identified (natural and induced) and both play significant roles in tuning down effector immune responses. Indeed, in parallel to thymus-derived natural Treg cells, induced regulatory T (iTreg) cells can develop in peripheral tissue under a variety of conditions such as antigen presentation under subimmunogenic or non inflammatory conditions. DCs and Treg cells are currently being considered as attractive targets towards manipulation of the immune system for therapeutic purposes. With this background, the special interest of our group is focused on the immunobiology of tolerogenic DCs and Treg cells and their suppressive functions. We are studying more particularly the beneficial effect of DCs and/or Tregs in experimental models of arthritis. Our aims are:
Vicente R. et al. Non-classical CD4+CD49b+ regulatoryT cells as a better alternative to conventional CD4+CD25+T cells to dampen arthritis severity. J. Immunol, in revision
Espinosa-Carrasco G. et al. Systemic LPS translocation activates cross-presenting dendritic cells but is dispensable for the breakdown of CD8+ T cell peripheral tolerance in irradiated mice. PLoS One. 2015 Jun 15;10(6)
Mebarek N. et al. Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells. Eur J Pharm Biopharm. 2015 May;92:216-27
Asnagli H et al. Type 1 regulatory T cells specific for collagen-type II as an efficient cell-based therapy in arthritis. Arthritis Research & Therapy. 2014, 16:R115 DOI: 10.1186/ar4567
Thiolat A et al. IL-6 Receptor Blockade Enhances CD39+ Regulatory T-Cell Development in Rheumatoid Arthritis and in Experimental Arthritis. Arthritis and Rheum 2013. Feb;66(2):273-83
Thiolat A. et al.. Reply To PMID 24504799 Arthritis & Rheumatol. 2014 Sep;66(9):2640-1
Spoerl D et al. The role of miR-155 in regulatory T cells and rheumatoid arthritis. Clin Immunol. 2013 Jul;148(1):56-65.
El Bannoudi H et al. DX5(+) CD4(+) T cells modulate CD4(+) T-cell response via inhibition of IL-12 production by dendritic cells. Eur J Immunol. 2013 Feb;43(2):439-46.
Présumey J et al. NAMPT/Visfatin expression by inflammatory monocytes mediates arthritis pathogenesis. Ann Rheum Dis. Oct;72(10):1717-24 (IF=8,72)
Charbonnier L-M et al. Adoptive transfer of IL-10-secreting CD4(+)CD49b(+) regulatory T cells suppresses ongoing arthritis. J Autoimmun. 2010 Jun;34(4):390-9
Charbonnier L-M et al. Immature dendritic cells suppress arthritis by in vivo expansion of CD49b+ regulatory T cells. J. Immunol 2006 177
Boudier A et al. Development of tripartite polyion micelles for efficient peptide delivery into dendritic cells without altering their plasticity. J Control Release. 2011 Sep 5;154(2):156-63.
Boudier A et al. The control of dendritic cell maturation by pH-sensitive polyion complex micelles. Biomaterials 2009, 30 233–241
More references, click on PubMed:
tel: +33 (0)4 67 33 57 21
T reg lymphocytes
Arthritis animal models
Immune response monitoring by cytometry 8 to 12 colors
Dendritic cell differentiation