Investigation of IL-9-producing cell types and their function in autoimmunity
Final Report Abstract
The analysis of interleukin-9 fate reporter mice established that the recently identified type 2 innate lymphoid cells (ILC2), and not T cells, are the major producers of this cytokine in vivo. The focus of the conducted project was the role of IL-9 and ILC2 during the lung stage of infection with Nippostrongylus brasiliensis, a lung-migrating parasite that induces substantial tissue damage. IL-9-receptor-deficient mice displayed reduced numbers of ILC2 in the lung following infection, resulting in impaired IL-5, IL-13 and amphiregulin levels, despite undiminished numbers of Th2 cells. As a consequence, the restoration of tissue integrity and lung function was strongly impaired in the absence of IL-9 signaling. ILC2, in contrast to Th2 cells, expressed high levels of the IL-9R and IL-9 signaling was crucial for the survival of activated ILC2 in vitro. Furthermore, ILC2 in the lungs of infected mice required the IL-9R to upregulate the antiapoptotic protein BCL-3 in vivo. This highlights a unique role for IL-9 as an autocrine amplifier of ILC2 function, promoting tissue repair in the recovery phase following helminth-induced lung inflammation.
Publications
- (2012) The many lives of IL-9: a question of survival? Nat Immunol 13:637-41
Wilhelm C, Turner JE, Van Snick J and Stockinger B
- (2013) Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14:372-9
Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM and Stockinger B
(See online at https://doi.org/10.1038/ni.2552)
