title: Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis.
abstract: Phospholipase Cgamma2 (PLCgamma2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCgamma2-deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-kappaB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCgamma2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCgamma2 markedly diminished RANKL-induced activation of NF-kappaB, AP-1, and NFATc1. Moreover, PLCgamma2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCgamma2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCgamma2 but not PLCgamma1 restores RANKL-mediated osteoclast differentiation of PLCgamma2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.
authors: Department of Pathology, University of Alabama at Birmingham and Veterans Affairs Medical Center, Birmingham, Alabama 35294, USA.
authors: Yabing
authors: Y
authors: Chen
authors: Xiaohong
authors: X
authors: Wang
authors: Lie
authors: L
authors: Di
authors: Guoping
authors: G
authors: Fu
authors: Yuhong
authors: Y
authors: Chen
authors: Li
authors: L
authors: Bai
authors: Jianzhong
authors: J
authors: Liu
authors: Xu
authors: X
authors: Feng
authors: Jay M
authors: JM
authors: McDonald
authors: Sue
authors: S
authors: Michalek
authors: Yinghong
authors: Y
authors: He
authors: Mei
authors: M
authors: Yu
authors: Yang-Xin
authors: YX
authors: Fu
authors: Renren
authors: R
authors: Wen
authors: Hui
authors: H
authors: Wu
authors: Demin
authors: D
authors: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D038081:Organogenesis; D010010:Osteoclasts / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D053245:RANK Ligand; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma