TY - JOUR
T1 - IL-4 and TGF-β1 counterbalance one another while regulating mast cell homeostasis
AU - Macey, Matthew R.
AU - Sturgill, Jamie L.
AU - Morales, Johanna K.
AU - Falanga, Yves T.
AU - Morales, Joshua
AU - Norton, Sarah K.
AU - Yerram, Nitin
AU - Shim, Hoon
AU - Fernando, Josephine
AU - Gifillan, Alasdair M.
AU - Gomez, Gregorio
AU - Schwartz, Lawrence
AU - Oskeritzian, Carole
AU - Spiegel, Sarah
AU - Conrad, Daniel
AU - Ryan, John J.
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.
AB - Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-β1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-b1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-β1 had balancing effects on mast cell survival, migration, and Fc«RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-β1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-β1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy.
UR - http://www.scopus.com/inward/record.url?scp=77954468083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954468083&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0903477
DO - 10.4049/jimmunol.0903477
M3 - Article
C2 - 20304823
AN - SCOPUS:77954468083
SN - 0022-1767
VL - 184
SP - 4688
EP - 4695
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -
