July 27, 2009 The cytokine IL-9 promotes a multiple sclerosis-like disease in mice, according to a new study by Nowak et al. published online on July 13th in the Journal of Experimental Medicine. In a related Commentary, Richard Locksley discusses the molecular and genetic regulation of cytokine production by CD4+ T helper (Th) cells and the plasticity among different Th subsets.
Since the late 1980s, when the concept of Th1 and -2 were first introduced, several new subsets have arisen, including Th17 cells and regulatory T (T reg) cells. Recent attention has focused on a putative new Th cell subset with the propensity to secrete IL-9. But whether these "Th9" cells are truly a unique subset or whether many Th cell subsets can produce IL-9 under the right circumstances has been a matter of debate.
Nowak and colleagues now show that a Th17-driven CNS disease was blunted in mice lacking IL-9. In vitro studies showed that IL-9 was produced primarily by Th17 and T reg cells—subsets that depend on TGF-beta for their differentiation. Thus IL-9 production may go hand-in-hand with the presence of TGF-beta rather than with a defined Th cell subset.
Locksley, R.M., et al. 2009. J. Exp. Med. doi:10.1084/jem.20091442
Nowak, E.C., et al. 2009. J. Exp. Med. doi:10.1084/jem.20090246
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