期刊
YEAR IN IMMUNOLOGY 2
卷 1183, 期 -, 页码 104-122出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1749-6632.2009.05122.x
关键词
c-kit; SCF; interleukin-6; Jagged-2; Notch; dendritic cells; adaptive immunity
类别
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL084932, R01HL069810, R01HL077430, R01HL060207] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI048927] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL060207, R01 HL069810, HL 060207, HL 077430, P50 HL084932, R01 HL077430, HL 069810, HL 084932] Funding Source: Medline
- NIAID NIH HHS [R01 AI048927, AI 048927] Funding Source: Medline
The binding of the receptor tyrosine kinase, c-kit, to its ligand, stem cell factor (SCF), mediates numerous biological functions. Important roles for c-kit in hematopoiesis, melanogenesis, erythropoiesis, spermatogenesis, and carcinogenesis are well documented. Similarly, activation of granulocytes, mast cells, and of eosinophils in particular, by c-kit ligation has long been known to result in degranulation with concomitant release of pro-inflammatory mediators, including cytokines. However, recent work from a number of laboratories, including our own, highlights previously unappreciated functions for c-kit in immunologic processes. These novel findings strongly suggest that signaling through the c-kit-SCF axis could have a significant impact on the pathogenesis of diseases associated with an immunologic component. In our own studies, c-kit upregulation on dendritic cells via T helper (Th)2- and Th17-inducing stimuli led to c-kit activation and immune skewing toward these T helper subsets and away from Th I responses. Others have shown that dendritic cell treatment with inhibitors of c-kit activation, such as imatinib mesylate (Gleevec), favored breaking of T-cell tolerance, skewing of responses toward production of Th I cytokines, and activation of natural killer cells. These data all indicate that deeper understanding of, and ability to control, the c-kit-SCF axis could lead to improved treatment modalities aimed at redirecting unwanted and/or deleterious immune responses in a wide variety of conditions.
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