Key words: cytokines, disease susceptibility
Our laboratory is interested in defining the mechanisms that control cell-specific cytokine gene expression patterns and how this influences disease susceptibility.
The precise temporal/spatial control of cytokine expression patterns is a key to host defense. Our laboratory is interested in defining the mechanisms that control cell-specific cytokine gene expression and how this influences disease susceptibility. In particular, we are interested in the immunoregulatory cytokine IL-10. To investigate cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC). Since human IL-10 is biologically active in the mouse, we can examine the in vivo function of cell-specific human IL-10 expression by reconstituting Il10-/- mice with the transgene (Il10-/-/hIL10BAC). We have found that in response to endotoxin challenge, Il10-/-/hIL10BAC mice regulate IL-10-target genes and normalize sensitivity to LPS toxicity via faithful human IL-10 expression from myeloid cells. Likewise, Tregs express human IL-10 in the gut and Il10-/-/hIL10BAC mice are resistant to colitis. However, other cell types only weakly express human IL-10 and fail to recapitulate IL-10-dependent phenotypes. Ongoing studies are characterizing the molecular events associated with cell- and tissue-specific IL-10 regulation.
Profile: Publications and Interests