Lipides, Nutrition, Cancer
SÉminaires LNC
AnnÉe 2018

Intervenant : Dr Sergei Nedospasov


Date :03 Septembre 2018 14h30
Lieu : Faculté de Médecine - Amphi Martin
Sujet :

TNF and cell type-restricted anti-cytokine therapy

Background: Cytokines are molecular mediators of intracellular communications selected by evolution to protect the host. Contributions of particular cytokines into pathogenesis of various diseases do not contradict their beneficial functions in other compartments of the body, including non-immune functions. Mouse studies based on reverse genetics suggested that many cytokines possess both redundant and unique features. Systemic therapeutic inhibition of cytokines may lead to unwanted side effects due to non-redundant protective functions of a given cytokine. For example, recent evidence suggests that TNF from specific cellular sources, both immune and non-immune, may play diverse and distinct roles in health and disease. In particular, we have evidence that TNF produced by T cells is protective in both autoimmune and infectious diseases, and part of this protective functions involve TNFR2 on Tregs. Since TNF produced by myeloid cells contributed to pathogenesis of experimental arthritis, we are developing and evaluating VHH-based bi-specific antibodies that with one arm would attach to the surface of myeloid cells, and with another arm can capture TNF released by these cells, preventing its dissemination and bioavailability. Our findings may serve as a basis for bioengineering of a novel type of cytokine inhibitors.


Selected publications:

1. Efimov, G.F. et al. Cell type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic source, PNAS (2016)

2. Kruglov, A.A. et al. Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis, Science (2013)

2. Grivennikov, S.I. et al. Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects, Immunity (2005)

Invitation: Oleg Demidov - UMR1231

Le séminaire aura lieu à la faculté de médecine -Amphi Martin - à 14h30

Renseignements - omicheau@u-bourgogne.fr Tel: 03 80 39 34 68