Interleukine-24 : rôle immunologique et mécanismes d'induction de mort cellulaire dans les lymphocytes B

Abstract : We have previously shown that Interleukin(IL)-24 a class-II cytokine of the IL-10 family has cytostatic and cytotoxic properties on normal and malignant human B-cells previously engaged into the cell cycle, but not on quiescent B-cells. IL-24 also inhibits the differentiation of germinal center B-cells in plasma cells in an in vitro model; the later was used to compare for the first time the transcriptome of B-cells cultured or not with IL-24 for 6 and 36h. Several "early" transcripts involved in DNA metabolism and replication were inhibited whereas that of Igf1 a molecule described as a B-cell growth factor was induced. We show herein that IgF1 has instead a proapoptotic role on B-cells at physiological concentrations. In contrast, several genes of the intrinsic apoptotic pathway were stimulated after 36h. This expression pattern was also found in CLL cells whether they were "IgVH mutated" or "unmutated", albeit with distinct kinetics from normal B-cells. In addition several genes belonging to the immune synapse and innate immunity were regulated by IL-24. These results disclose additional, possibly immunoregulatory properties, for IL-24 than its already described cytostatic and potentially anti-tumoral effects
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Nader Hadife. Interleukine-24 : rôle immunologique et mécanismes d'induction de mort cellulaire dans les lymphocytes B. Médecine humaine et pathologie. Université de Lorraine, 2013. Français. ⟨NNT : 2013LORR0018⟩. ⟨tel-01749415⟩

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