Th2 immunity, once established, can exert a broad influence on many cell types to form a network of effector cells, including Th2 cytokine-producing basophils, mast cells and eosinophils. However, how Th2 cells communicate with bone marrow progenitors cells to further enhance type-2 immune responses has not been explored extensively. We are exmaning three possible mechanisms. First, circulating Th2 cytokines can enter the bone marrow to exert their biological activities directly on various hematopoietic progenitors. Second, bone marrow progenitors can be recruited into the lung, where they undergo maturation and expansion. Finally, memory Th2 cells can enter the blood stream and reside in the bone marrow.
While we haven’t obtained direct evidence to support the first possiblity (Th2 cytokines can circulate into the bone marrow), we have demonstrated that Th2 cytokines, such as IL-3, IL-4, and IL-5, can direct bone marrow progenitors to differentiate eosinophils and basophils that can produce Th2 cytokines (Zhu, JI, 2004). We found that IL-3 can induce dramatic expansion of i2GMPs and basophil lineage-restricted progenitors in vivo (Ohmori, JI 2009). We demonstrated that IL-5 drives bone marrow progenitor cells primarily to differentiate into Th2 cytokine-producing eosinophils dependent upon STAT5 (Zhu, JI Cutting edge) and transcription factor GATA1. Currently, we are using GATA1 mutants to determine how GATA1 regulates the Il4 gene in eosinophils. Currently, we are testing the above-mentioned second possibility.
In summary, we have found a niche that defines our lab. In that niche we will be productive for many years to come.
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