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

Oriss, Timothy B.; Krishnamoorthy, Nandini; Ray, Prabir; Ray, Anuradha

Current Opinion in Allergy & Clinical Immunology: February 2014 - Volume 14 - Issue 1 - p 7–12
doi: 10.1097/ACI.0000000000000019
RHINITIS, SINUSITIS AND UPPER AIRWAY DISEASE: Edited by Ruby Pawankar and David P. Skoner

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.

aDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

bBrigham and Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts

cDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Correspondence to Anuradha Ray, PhD, NW628 MUH, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA. Tel: +1 412 802 3191; fax: +1 412 692 3219; e-mail: raya@pitt.edu

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