Title

 

Authors

L. Cavone

Dept. of Preclinical and Clinical Pharmacology, University of Florence
PhD Course: Pharmacology and Toxicology

 

Abstract

T lymphocytes play crucial roles in many different  immune responses. Effector T helper (Th) cells derive from progenitor naïve CD4+ T cells, after maturational process induced by professional antigen presenting cells [i.e. dendritic cells (DCs)]. CD4+ T cells may differentiate into Th1, Th2, Th17 phenotypes (the effector Th cell triade) or evolve into the inducible regulatory T (Treg) lineage, with immunomodulatory functions.  The different polarization of naïve CD4+ cells depends on the specific antigen presentation contest established by DCs. Numerous reports show that while fully-mature DC (high expression of co-stimulatory molecules an production of pro-inflammatory cytokine) induce differentiation toward the Th triade, partially-mature DCs are able to induce differentiation toward Treg. Since our group recently demonstrated thatPARP-1 activity is instrumental for maturation of DCs  and DC-dependent lymphocyte proliferation,we wondered whether PARP-1 inhibitor administration would induce Treg expansion in a mouse model of Ovalbumin (OVA) immunization. In this presentation we will discuss the effect of the two structurally unrelated PARP-1 inhibitors phenathridinone (PHE) and PJ34 on DC maturation (expression of co-stimulatory molecules and cytokines production) in lymph nodes of OVA immunized mice. We will also present data regarding the increased number Treg cells in drug injected  mice and on the ability of these cells to reduce antigen specific proliferation of Th cells. Finally, the ability of DCs harvested from lymph nodes of animals immunized and treated with PHE and PJ34 to induce a Treg phenotype of naïve CD4+ will be shown.