MOLECULAR MECHANISMS OF cytokine GENE EXPRESSION and their immunological activities IN auto- and tumor-immunity
Interleukin-12 (IL-12) is a heterodimeric, proinflammatory cytokine produced by phagocytic cells and plays a critical role in the activation and function of antigen-presenting cells and effector lymphocytes during microbial infection. Interleukin-10 (IL-10) is a homodimeric cytokine produced mainly by monocytes/macrophages, activated T and B lymphocytes. IL-10 has potent anti-inflammatory and immunosuppressive activities on myeloid cell functions while it also exerts immune stimulatory effects on B cells for proliferation, differentiation and antibody production. It is a pivotal homeostatic regulator of immune reactivity. The production of IL-12 and IL-10 by phagocytic and antigen-presenting cells is regulated in opposite manners during innate and adaptive immune responses. The understanding of the molecular mechanisms controlling the gene expression of IL-12 and IL-10 in interactions between pathogens and the immune system is essential to efforts to develop therapeutic strategies for infectious, malignant and autoimmune diseases. We are currently investigating in the following areas:
I. Molecular mechanisms of pathogen/antigen-mediated regulation of IL-12 and IL-10 gene expression in macrophages and dendritic cells.
II. Molecular mechanisms of the regulation of IL-12 and IL-10 gene expression during phagocytosis of apoptotic cells by macrophages and dendritic cells.
III. Molecular mechanisms of the regulation of IL-10 gene expression by the Crohn’s disease-associated mutants of nucleotide-binding oligomerization domain 2 (Nod2).
IV. Identification and characterization of a novel B-lymphocyte derived soluble factor that inhibits IL-12 production by antigen-presenting cells and IL-12-mediated anti-tumor activity.