Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata

BACKGROUND Toll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management. METHODS Gene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs. RESULTS All TLRs (TLRs 1-10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p < 0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p < 0.05). Whereas, TGF-β gene expression in patients' PBMCs and TGF-β protein level in patients' sera were significantly lower as compared with their controls (p < 0.05). CONCLUSION This is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata. GENERAL SIGNIFICANCE Targeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders.