Modulating autoimmunity: Pick your P13 kinase

Article Abstract:

A pharmacological inhibitor is presented that selectively targets the phosphatidylinositol 3-kinase (PI3K) gamma complex and effectively reduces severity of disease in mouse models of arthritis and lupus. The PI3K enzyme family is divided into three classes according to members' structural domains, modes of regulation and substrate specificity.

Author: Ohashi, Pamela S., Woodgett, James R.
Research and Development in the Physical, Engineering, and Life Sciences, Research and Testing Services, Arthritis R&D, Arthritis research, Autoimmunity, Phosphatidylinositol

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Blockade of P13Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis

Article Abstract:

The identification and development of specific, selective and orally active small-molecule inhibitors of phosphoinositide 3-kinases gamma (PI3Kgamma) is described. Results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Author: Martin, Thierry, Camps, Montserrat, Hirsch, Emilio, Perrin, Dominique, Wymann, Matthias P., Schwarz, Matthias K., Ruckle, Thomas, Rommel, Christian, Francon, Bernard, Gillieron, Corine, Gretener, Denise, Hong Ji, Chabert, Christian, Cirillo, Rocco, Ardissone, Vittoria, Ferrandi, Chiara, Leroy, Didier, Rintelen, Felix, Shaw, Jeffrey, Vitte, Pierre-Alain
Care and treatment, Rheumatoid arthritis, Phosphoinositides

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TCR affinity and negative regulation limit autoimmunity

Article Abstract:

A model is developed to analyze how the affinity of the T-cell receptor (TCR) for the activating agent influences autoimmunity. The study provides further support to the notion that most autoimmune diseases are a combination of genetic and environmental factors.

Author: Ohashi, Pamela S., Penninger, Josef M., Odermatt, Bernhard, Moskophidis, Demetrius, Gascoigne, Nicholas R.J., Elford, Alisha R., Gronski, Matthew A., Boulter, Jonathan M., Nguyen, Linh T., Holmberg, Kaisa, Deenick, Elissa K., Kim, Hee, O., Gallimore, Awen
Causes of, Autoimmune diseases, Antigen receptors, T cell, T cell antigen receptors, Immunopathology

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Subjects list: Research, United States, Protein kinases, Phosphatidylinositols
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