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Blood, 1 February 2004, Vol. 103, No. 3, pp. 843-851.
Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-05-1557.
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HEMATOPOIESIS
Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis
Mark J. Osborn,
Patricia L. Ryan,
Nicole Kirchhof,
Angela Panoskaltsis-Mortari,
Frank Mortari, and
Kim-Sue R. S. Tudor
From the Department of Laboratory Medicine and Pathology, Division of Medical Technology, University of Minnesota, Minneapolis; Veterinary Diagnostic Laboratory, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; University of Minnesota Cancer Center Histopathology Core, Minneapolis; and R & D Systems, Inc, Minneapolis, MN.
The role of thymic stromal cell–derived lymphopoietin (TSLP) in regulating hematopoiesis is poorly characterized, so we investigated its regulatory effects in vivo using TSLP transgenic mice. Overexpression of TSLP disrupted hematopoietic homeostasis by causing imbalances in lymphopoiesis and myelopoiesis. Mice harboring a TSLP transgene had 5- to 700-fold fewer B and T precursors and no detectable pre-B lymphocyte colonyforming activity in the marrow or spleen. Conversely, TSLP transgenic mice possessed 15 to 20 times more splenic myeloid precursors than their littermates, and progenitor activity of the granulocyteerythrocyte-macrophage-megakaryocyte colony-forming units was significantly elevated. The arrest in lymphopoiesis and the expansion of myeloid progenitor cells in TSLP transgenic mice suggest that TSLP has negative and positive regulatory effects on lymphoid and myeloid development, respectively.
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