Blockade of transforming growth factor β/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity

A Nakao, S Miike, M Hatano, K Okumura… - The Journal of …, 2000 - rupress.org
A Nakao, S Miike, M Hatano, K Okumura, T Tokuhisa, C Ra, I Iwamoto
The Journal of experimental medicine, 2000rupress.org
Transforming growth factor (TGF)-β has been implicated in immunosuppression. However, it
remains obscure whether regulation of T cells by TGF-β contributes to the
immunosuppression in vivo. To address this issue, we developed transgenic mice
expressing Smad7, an intracellular antagonist of TGF-β/Smad signaling, selectively in
mature T cells using a plasmid construct coding a promoter element (the distal lck promoter)
that directs high expression in peripheral T cells. Peripheral T cells were not growth inhibited …
Transforming growth factor (TGF)-β has been implicated in immunosuppression. However, it remains obscure whether regulation of T cells by TGF-β contributes to the immunosuppression in vivo. To address this issue, we developed transgenic mice expressing Smad7, an intracellular antagonist of TGF-β/Smad signaling, selectively in mature T cells using a plasmid construct coding a promoter element (the distal lck promoter) that directs high expression in peripheral T cells. Peripheral T cells were not growth inhibited by TGF-β in Smad7 transgenic mice. Although Smad7 transgenic mice did not spontaneously show a specific phenotype, antigen-induced airway inflammation and airway reactivity were enhanced in Smad7 transgenic mice associated with high production of both T helper cell type 1 (Th1) and Th2 cytokines. Thus, blockade of TGF-β/Smad signaling in mature T cells by expression of Smad7 enhanced airway inflammation and airway reactivity, suggesting that regulation of T cells by TGF-β was crucial for negative regulation of the inflammatory (immune) response. Our findings also implicated TGF-β/Smad signaling in mature T cells as a regulatory component of allergic asthma.
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