Trib3 is regulated by IL-3 and affects bone marrow-derived mast cell survival and function.

ABSTRACT

Mast cells are the principal effectors of IgE-mediated immune responses, including allergic reactions. Tribbles homolog 3 (Trib3) encodes a pseudokinase implicated in the cellular stress response and has been linked to inflammation in certain situations. Here we report the role of Trib3 in mouse bone marrow-derived mast cells (BMMCs). Our results show that Trib3 mRNA expression in BMMCs is positively regulated by the growth factor interleukin (IL)-3. BMMCs originating from Trib3 knockout mice demonstrate unaltered differentiation kinetics and cell surface expression of mast cell markers. When challenged with transient IL-3 deprivation, Trib3-deficient BMMCs display delayed recovery, and during prolonged IL-3 starvation, cell death is accelerated in Trib3-null cultures. IgE-dependent and pharmacologically induced degranulation is impaired in Trib3-deficient BMMCs, as is activation-induced cytokine mRNA expression. Thus, Trib3 contributes to the survival and activity of primary cultured mast cells, which suggests a role for Trib3 in the modulation of the immune response.