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Current Opinion in Allergy & Clinical Immunology:
doi: 10.1097/ACI.0000000000000019
RHINITIS, SINUSITIS AND UPPER AIRWAY DISEASE: Edited by Ruby Pawankar and David P. Skoner

Dendritic cell c-kit signaling and adaptive immunity: implications for the upper airways

Oriss, Timothy B.a; Krishnamoorthy, Nandinib; Ray, Prabira,c; Ray, Anuradhaa,c

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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.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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