Cytokines represent a large number of secreted proteins that regulate cell growth and differentiation. These factors are especially important in regulating immune and inflammatory responses, regulating lymphoid development and differentiation. Cytokines also regulate immune homeostasis, tolerance, and memory. Not surprisingly, cytokines are critical in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and psoriasis. Understanding the molecular basis of cytokine action provides important insights into the pathogenesis of immune-mediated disease and offers new therapeutic targets. ? We discovered Jak3, a kinase essential for signaling by cytokines that bind the common gamma chain, gc (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21). We found that mutation of Jak3 results in a primary immunodeficiency disorder termed severe combined immunodeficiency (SCID). We have a clinical protocol that allows us to evaluate patients with suspected Jak3 deficiency. No new patients were evaluated this year.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2008
Total Cost
$26,035
Indirect Cost
Name
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Mielke, Lisa A; Elkins, Karen L; Wei, Lai et al. (2009) Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production. J Immunol 183:7984-93
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Bluestone, Jeffrey A; Mackay, Charles R; O'Shea, John J et al. (2009) The functional plasticity of T cell subsets. Nat Rev Immunol 9:811-6
Pesu, Marko; Laurence, Arian; Kishore, Nandini et al. (2008) Therapeutic targeting of Janus kinases. Immunol Rev 223:132-42