MMP19 is essential for T cell development and T cell-mediated cutaneous immune responses.
Matrix metalloproteinase-19 (MMP19) affects cell proliferation, adhesion, and migration in vitro but its physiological role in vivo is poorly understood. To determine the function of MMP19, we generated mice deficient for MMP19 by disrupting the catalytic domain of mmp19 gene. Although MMP19-deficient mice do not show overt developmental and morphological abnormalities they display a distinct physiological phenotype. In a model of contact hypersensitivity (CHS) MMP19-deficient mice showed impaired T cell-mediated immune reaction that was characterized by limited influx of inflammatory cells, low proliferation of keratinocytes, and reduced number of activated CD8(+) T cells in draining lymph nodes. In the inflamed tissue, the low number of CD8(+) T cells in MMP19-deficient mice correlated with low amounts of proinflammatory cytokines, especially lymphotactin and interferon-inducible T cell alpha chemoattractant (I-TAC). Further analyses showed that T cell populations in the blood of immature, unsensitized mice were diminished and that this alteration originated from an altered maturation of thymocytes. In the thymus, thymocytes exhibited low proliferation rates and the number of CD4(+)CD8(+) double-positive cells was remarkably augmented. Based on the phenotype of MMP19-deficient mice we propose that MMP19 is an important factor in cutaneous immune responses and influences the development of T cells.
Institute of Biotechnology, Prague, Czech Republic.
Inken M
IM
Beck
René
R
Rückert
Katja
K
Brandt
Markus S
MS
Mueller
Thorsten
T
Sadowski
Rena
R
Brauer
Peter
P
Schirmacher
Rolf
R
Mentlein
Radislav
R
Sedlacek
D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D005434:Flow Cytometry; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*
D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19