Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b

Article Abstract:

It has been possible to identify the development of spontaneous autoimmunity in cbl-b-deficient mice. Age, environmental factors and genetic background determine the onset and extent of spontaneous autoimmunity. It has been shown that Cbl-b is involved in key events of lymphocyte activation, being a negative regulator of T- and B-cell activation and regulating the triggering threshold of antigen receptors in T and B cells. Resting cbl-b-/- lymphocytes hyperproliferate upon antigen receptor stimulation, and cbl-b-/- T cells show specific hyperproduction of the T-cell growth factor interleukin-2.

author: Bachmaier, Kurt, Krawczyk, Connie, Kozieradzki, Ivona, Kong, Young-Yun, Sasaki, Takeiko, Oliveira-dos-Santos, Antonio, Itie, Annick, Le, Jenny, Ohashi, Pamela S., Sarosi, Ildiko, Nishina, Hiroshi, Lipkowitz, Stan, Penninger, Josef
Autoimmunity, Lymphocyte transformation

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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis

Article Abstract:

The process of morphogenesis and remodelling of bone is controlled physiologically with the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. It has been found that the new TNF-family molecule osteoprotegerin ligand (OPGL) can activate mature osteoclasts and mediate osteoclastogenesis in the presence of colony-stimulating factor-1 (CSF-1). Studies have shown that the molecule is an important factor in early differentiation of thymocytes and B-cell precursors, and opgl-1- mice were found to lack lymph nodes.

author: Kong, Young-Yun, Itie, Annick, Sarosi, Ildiko, Penninger, Josef, Wakeham, Andrew, Mak, Tak W., Lacey, David L., Boyle, William J., Yoshida, Hiroki, Oliveira-dos-Santos, Antonio J., Morony, Sean, Khoo, Wilson, Dunstan, Colin R., Capparelli, Casey, Tan, Hong-Lin, Timms,Emma, Van, Gwyneth
Observations, Morphogenesis, Tumor necrosis factor

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Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand

Article Abstract:

Activated T cells can control systemic and local bone loss through osteoprotegerin ligand (OPGL). These cells produce OPGL and can directly prompt osteoclastogenesis in vivo. It has been established that six out of seven spontaneously arising T-cell lymphomas in mice express high levels of OPGL on T-cell surfaces. These lymphoma cells can directly support in vitro osteoclastogenesis. Inhibition of OPGL function could improve many osteopenic conditions.

author: Kong, Young-Yun, Ohashi, Pamela S., Penninger, Josef, Li, Ji, Lacey, David L., Boyle, William J., Tafuri, Anna, McCabe, Susan, Nguyen, Linh T., Morony, Sean, Wong, Thomas, Capparelli, Casey, Van, Gwyneth, Feige, Ulrich, Sarosi, Iidiko, Bolon, Brad, Elliott, Robin, Campagnuolo, Giuseppe, Moran, Erika, Bogoch, Earl R., Fish, Eleanor
Causes of, Arthritis, T cells

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subjects list: Research
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