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Signaling of c‐kit in dendritic cells influences adaptive immunity
Author(s) -
Ray Prabir,
Krishnamoorthy Nandini,
Oriss Timothy B.,
Ray Anuradha
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05122.x
Subject(s) - stem cell factor , proto oncogene proteins c kit , immune system , immunology , degranulation , plasmacytoid dendritic cell , biology , cytokine , imatinib mesylate , dendritic cell , acquired immune system , microbiology and biotechnology , haematopoiesis , cancer research , receptor , stem cell , imatinib , biochemistry , myeloid leukemia
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 Th1 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 Th1 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.