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Investigating the identity and functions of dendritic cell types across tissues and species.

. © Inra, Haymanj
Publié le 21/12/2018
Mots-clés : CONFÉRENCES

Jeudi 10 janvier 2019

Amphithéâtre Jacques Poly, bât. 440

INRA IdF-Jouy-en-Josas

Résumé

Among professional antigen presenting cells (APCs), dendritic cells (DCs) are the most potent for the activation of naïve T cells upon their first encounter with their cognate antigen, a process coined T cell priming. In addition, data are accumulating to show that DCs promote T cell functions not only during priming, but all along their life cycle, including for the maintenance of their effector functions in tumors or infected tissues, for memory induction as well as for the recall responses upon secondary encounters with pathogens. Therefore, DCs are considered as extremely interesting targets for the development of innovative vaccines or immunotherapies against cancer or infections by intracellular pathogens. In addition, DCs control the balance between tolerance and immunity; thus, it should also be possible to harness them to dampen deleterious immune responses as occurs in autoimmune or inflammatory diseases. More generally, DCs can polarize T cell responses towards a variety of functions, depending of the nature of the threat to be faced by the organism. This is achieved through integration by the DCs of a variety of input signals that they can sense in a given pathophysiological context and which determine their activation state, leading to the delivery of a matched combination of output signals to T cells to promote their activation in a way properly tailored for protection. This plasticity in DC functions also results from the existence of distinct types of DCs that each express specific arrays of innate immune recognition receptors and are specialized for the delivery of different output signals. Therefore, advancing towards the goal of harnessing DC functions to promote health over disease in humans and animals of economic interest requires first to better identify DC types and activation states, their functions and their molecular regulation. This can be most efficiently achieved by a global comparative immunology approach, building on comparative gene expression profiling of immune cells across tissues and species, to identify conserved gene modules universally characterizing DC types and activation states, instructing the engineering and study of dedicated mutant mouse models to test hypotheses on DC functions, with further validation in other species first upon development and characterization of in vitro models that better match the DC types which are present in lymphoid organs and orchestrate immune responses in vivo, and then upon in vivo studies whenever possible. 

Invité par Isabelle Schwartz, unité VIM Virologie et Immunologie Moléculaires (Inra UR 892-VIM)