Phospholipase Cγ2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis

Academic Article

Abstract

  • Phospholipase Cγ2 (PLCγ2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCγ2- deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-κB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCγ2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCγ2 markedly diminished RANKL-induced activation of NF-κB, AP-1, and NFATc1. Moreover, PLCγ2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCγ2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCγ2 but not PLCγ1 restores RANKL-mediated osteoclast differentiation of PLCγ2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCγ2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Chen Y; Wang X; Di L; Fu G; Chen Y; Bai L; Liu J; Feng X; McDonald JM; Michalek S
  • Start Page

  • 29593
  • End Page

  • 29601
  • Volume

  • 283
  • Issue

  • 43