1).7 The type I collagenase, matrix metalloproteinase (MMP)-13 (but not MMP-2, MMP-8, or MMP-14), was identified as a major macrophage-derived matrix degrading enzyme in this resolving process (Fig. 1).8 The investigators did not, however, investigate the expression of CD11c or MHC II in the cells they ablated. In studies published in this current addition of Hepatology, Jiao et al.9 now report a critical role for DCs in resolution of fibrosis following CCl4-mediated liver fibrosis and identify MMP-9 as a key effector enzyme in DCs (Fig. 1). MMP-9

is a gelatinase that cleaves type IV collagen and Cisplatin ic50 elastin, also constituents of pathological matrix, and is widely reported as a major effector molecule in macrophages.10 In order to draw these conclusions the investigators used a different transgenic mouse to ablate myeloid cells, CD11c-DTR (DTR under regulation of the CD11c promoter),11 and they focused on the resolution phase after CCl4-mediated fibrosis during which accumulated scar tissue is resorbed and remodeled. To the uninitiated, these investigations might seem to have uncovered a completely novel pathway of resolution

of fibrosis. However, we now appreciate that CD11c and CD11b are poor discriminators of cells with DC functions and macrophage functions (Table 2). Moreover, in peripheral organs Stem Cells antagonist such as the liver it seems that the vast majority of myeloid cells express both CD11b and CD11c to varying degrees.6, 9, 12 Therefore, it may simply be that the investigators have unwittingly ablated the same cells in the liver that the studies from 2005 ablated and have chosen to call them DCs, whereas the investigators in 2005 chose to call them macrophages. In keeping with that line of thought, the processes of digesting, phagocytosing, and clearance of matrix and its constituents are widely recognized as macrophage-type functions rather than DC-type functions

in many organs (Table 1), and MMP-9 is widely reported in the literature as a macrophage effector, not a DC effector molecule.10 As such, therefore, the cells they have identified are not DCs, rather they are CD11c-DTR-sensitive macrophages. However, if we step back from the controversies and problems with nomenclature MCE公司 of peripheral organ tissue effector cells, the investigators have identified a CD11b+, CD11chighCD11c-DTR-sensitive subpopulation of liver inflammatory myeloid cells (IMCs) that specifically are responsible for resolution of scarring, in part by producing MMP-9 (Fig. 1). They clearly identify this subpopulation in the resolving liver among other myeloid leukocytes that are presumably either not directly contributing to scar resolution or are contributing to scar resolution by other mechanisms (it is not possible to determine to what extent fibrosis-resolution is halted by ablation of this subpopulation).