| First Author | Hidano S | Year | 2012 |
| Journal | Int Immunol | Volume | 24 |
| Issue | 11 | Pages | 719-27 |
| PubMed ID | 22875843 | Mgi Jnum | J:189836 |
| Mgi Id | MGI:5447110 | Doi | 10.1093/intimm/dxs072 |
| Citation | Hidano S, et al. (2012) SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated activation of basophils. Int Immunol 24(11):719-27 |
| abstractText | Basophils have been reported to play a critical role in allergic inflammation by secreting IL-4 in response to IL-3 or high-affinity IgE receptor (FcepsilonRI)-cross-linking. However, the signaling pathways downstream of FcepsilonRI and the IL-3 receptor in basophils have yet to be determined. In the present study, we used mice deficient in SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76kDa) to demonstrate critical functions of this adaptor molecule in transducing FcepsilonRI- and IL-3 receptor-mediated signals that induce basophil activation. Although SLP-76 was dispensable for in vivo differentiation, as well as IL-3-induced in vitro proliferation of basophils, IL-4 production induced by both stimuli was completely ablated by SLP-76 deficiency. Biochemical analyses revealed that IL-3-induced phosphorylation of phospholipase C (PLC) gamma2 and Akt, but not STAT5, was severely reduced in SLP-76-deficient basophils, whereas FcepsilonRI cross-linking phosphorylation of PLCgamma2, but not Akt, was abrogated by SLP-76 deficiency, suggesting important differences in the requirement of SLP-76 for Akt activation between FcepsilonRI- and IL-3 receptor-mediated signaling pathways in basophils. Because IL-3-induced IL-4 production was sensitive to calcineurin inhibitors and an intracellular calcium chelator, in addition to PI3K inhibitors, SLP-76 appears to regulate FcepsilonRI- and IL-3 receptor-induced IL-4 production via mediating PLCgamma2 activation in basophils. Taken together, these findings indicate that SLP-76 is an essential signaling component for basophil activation downstream of both FcepsilonRI and the IL-3 receptor. |
