Dendritic cell c-kit signaling and adaptive immunity
Year: 2013
Type: article
Abstract: PURPOSE OF REVIEW: 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 mast cells and eosinophils by c-kit ligation has long been known to result in degranulation with concomitant release of pro-inflammatory mediators including cytokines. This review will highlight a recently discovered function of c-kit in regulating the adaptive immune responses with relevance to allergic diseases. RECENT FINDINGS: Recent studies in a number of laboratories including our own highlight the previously unappreciated functions for c-kit in immunological processes. Increased expression of c-kit and its ligand, SCF, on dendritic cells by Th2/Th17-inducing stimuli leads to c-kit activation and immune skewing toward these subsets and away from Th1 responses. Treatment of dendritic cells with inhibitors of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell tolerance, skewing of responses toward Th1, and activation of natural killer cells. SUMMARY: Taken together, these observations suggest that the c-kit/SCF axis may be a useful target for redirecting deleterious immune responses in various disease settings, including allergic diseases that are often associated with Th2 and Th17 responses.
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1342907914, G1701237807, DC-T Cell Interactions in Pulmonary Immune Responses, G2112542703, Mechanisms of Antigen-Induced Tolerance in the Lung, G3508156052, G3827547380, Targeting c-kit in Dendritic Cells to Control allergic Immune Responses, Basic and Translational Studies of Cystic Fibrosis, G6258982096, Understanding Protective Immunoregulatory Mechanisms in the Infant Lung, G886671910
OpenAlex ID: W2086102465