IL-6 type cytokines, especially IL-6, IL-11, OSM and LIF in conjunction with their shared common receptor subunit gp130 play an important role for the regulation of organism homeostasis. Gp130 thereby acts as the membrane bound part of the receptor complex, that upon homo- or hetero-dimerization induces the phosphorylation of its intracellular tyrosines activating Ras- or STAT1/3- dependent signalling cascades. The general importance of gp130 and dependent processes becomes evident already during the phase of embryonic development. Gp130 knockout embryos suffer from a severely restricted haematopoiesis as well as from an impaired hepatic development and subsequently die in utero. This functionally distinguishes gp130 from its multiple ligands, which show redundant biological functions. Therefore, the phenotype of individual cytokine-knockout mice is often more subtle and less severe than deletion of their receptors. Introduction of conditional gp130-knockout mice by Betz et al provided initial insights into the regulatory role of gp130 in haematopoiesis. Those mice showed a spontaneous mild thrombocytopenia, while leukocyte numbers were increased. The relative amount of T-cells was also reduced. After the induction of chemically induced BM injury those mice showed a delayed recovery in erythrocytes and platelets together with a 40% reduction of haematopoietic progenitors. In contrast, mice overexpressing the gp130 ligands IL-6 or LIF displayed a hyperproliferation of haematopoietic cells and developed splenomegaly, plasmocytosis, thrombocytosis and extramedullar haematopoiesis. It was shown that IL-6 and LIF synergize with IL-3 and stem cell factor, which are important for the Gefitinib EGFR/HER2 inhibitor integrity of haematopoietic progenitor cells. In an effort to delineate the dichotomy of gp130-dependent intracellular signalling, that leads to the activation of Ras- or STAT-pathways respectively, partial gp130- knockin/knockout mice were created. Mice lacking the 4 distal tyrosine residues of the cytoplasmic domain of gp130, which constitute the STAT1/3 binding sites, showed elevated numbers of BM precursors and reduced platelet counts. On the contrary, mice carrying a point mutation in gp130 tyrosine-757 display elevated basal STAT3 activation but are deficient for gp130-Ras-signalling. These mice develop a broad spectrum of haematopoietic abnormalities, including splenomegaly, lymphadenopathy, and thrombocytosis. Whereas the role of gp130-signals in steady state haematopoiesis has been well characterized, its functions in BMT remain unclear. There is evidence, that gp130 is important in endothelial cells of BM recipient mice, yet the more pressing issue, whether it plays a role within the donor cell compartment is still unresolved. This is especially important since donor cells could be easily analysed and conditioned prior to transplantation. This prompted us to carefully dissect the function of gp130 in BM donor cells during the process of engraftment and proliferation. We have recently demonstrated the contribution of the different gp130-dependent signalling.