THE ROLE OF IL-27P28 ON TYPE I INTERFERON REGULATION IN ANTIGEN-PRESENTING CELLS UPON LPS STIMULATION

Abstract

TYPE I INTERFERONS (IFNS) ARE EXPRESSED BY MANY CELL TYPES FOLLOWING VIRAL AND BACTERIAL INFECTIONS, AND INDUCE DOWNSTREAM IFN-STIMULATED GENES (ISGS), SUCH AS ANTI-VIRAL GENES. TIGHTLY CONTROLLED UP-REGULATION OF TONIC TYPE I IFN SIGNALING IS REQUIRED TO MEDIATE HOST CELL RESPONSES TO PATHOGENS AND RESTRAIN INFLAMMATION UNDER HOMEOSTATIC CONDITIONS. THEREFORE, UNDERSTANDING THE MECHANISM OF TYPE I IFN INDUCTION IN IMMUNE RESPONSE IS VERY IMPORTANT. ENHANCEMENT OF TYPE I IFN RESPONSES IN VIRUS-CHALLENGED FIBROBLASTS AND DENDRITIC CELLS IS MEDIATED BY WELL-DEFINED PATHWAYS, BUT THE MECHANISMS UNDERPINNING MACROPHAGE IFN-? RESPONSES TO BACTERIAL LIPOPOLYSACCHARIDE REMAIN UNCLEAR. IN FIBROBLASTS AND DENDRITIC CELLS, TYPE I IFNS HAVE BEEN DEMONSTRATED TO INDUCE FURTHER TYPE I IFN EXPRESSION VIA AN AUTOCRINE/PARACRINE POSITIVE FEEDBACK LOOP MEDIATED BY PARTICULAR INTERFERON REGULATORY FACTORS (IRFS). IN MACROPHAGES, AUTOCRINE/PARACRINE TYPE I IFN SIGNALING HAVE BEEN SHOWN TO BE IMPORTANT FO