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Role of DC and Macrophages in the Maintenance of Barrier Integrity:

       One of the focuses of our laboratory in the recent years has been to identify the tissue-derived factors that contribute to macrophage and DC survival and function in barrier tissues.  For example, we showed that the newly identified IL-34 is produced by keratinocytes and neurons in mice and human and is critical for the maintenance of both microglia and Langerhans cell homeostasis in tissue (Greter et al. Immunity 2012). More recently, we found that GM-CSF is produced in the steady state gut by innate lymphocytes in response to microbial signals and contribute to the maintenance of macrophage and DC regulatory function and maintenance of Treg homeostasis (Mortha et al. Science 2014). Thus, in addition to understanding the cell-intrinsic regulation of phagocyte development and function, our goal is to continue deciphering the cell-extrinsic programs that promote phagocyte homeostasis in barrier tissues, as we believe that these factors are critical in the maintenance of organismal integrity and that defects in these regulatory programs may contribute to the pathogenesis of inflammatory diseases.