Department of Infectious Diseases
Immunology | Infectious Diseases | Virology
Regulation of host defense and tolerance by Stat transcription factors
My research is devoted to understanding the mechanisms that regulate host defense on one hand and tolerance on the other. Signal transducers and activators of transcription (Stats) are a family latent cytosolic transcription factors activated by cytokins and growth factors that regulate this pivotal balance. Activated Stats impart distinct effect or functions on developing naive CD4+ T cells to tune adaptive immune responses. The activation of Stat4 by interleukin 12 (IL-12) and related cytokines is critically important in the defense against intracellular pathogens through the Stat4-dependent induction of the potent inflammatory cytokine, interferon-y (IFN-y). This pathway is particularly relevant in light of the recent escalation in the incidence of multi-drug resistant forms of tuberculosis, a leading cause of infectious death. In order to better understand the physiologic functions of Stat4 as they pertain to cell-mediated immunity, we have performed microarray analysis to identify genes regulated by IL-12. Among many IL-12 inductible genes, we identified the mitogene- activated protein kinase Tpl2 (aka MAP3K8)as a bonafide Stat4 target gene. Current research is aimed at understanding the contribution(s) of Tpl2and other Stat4 target genes to the regulation of T helper cell development and host immune responses to infectious and autoimmune disease settings.