Abstract
The objective of this study was to investigate the frequency and functionality of DCs and its associated stimulatory and inhibitory markers in the pathogenesis of PV Active PV patients (n = 30) having both skin and oral lesions, and 30 healthy controls were recruited in the study. The frequency of DCs was determined by flow cytometry followed by the primary culture by using recombinant IL-4 (250 IU/ml) and GM-CSF (600 IU/ml). The culture supernatant was used for ELISA. RNA was isolated from sorted DCs and used for the mRNA expression of DC-associated stimulatory (CD40 and CD80) and inhibitory (PSGL1 and ILT3) markers. Tissue localization of Langerhans cells was done by immunohistochemistry. In this study, altered frequency of myeloid DC (mDC) and plasmacytoid DC (pDC) was seen in the circulation of PV patients. The primary culture of patient-derived DCs showed anomalous cytokine profiling. In the culture supernatant of DCs, elevated levels of TNF-ɑ and IL-12 were detected in PV patients. Meanwhile, reverse trend was found in the case of IFN-ɑ and IL-10 cytokine levels. Similarly, a discrepancy in the expression of DC-associated stimulatory (CD40 and CD80) and inhibitory (PSGL1 and ILT3) markers suggested their possible involvement in the immunopathogenesis of PV. An elevated number of tissue localizing Langerhans cells was also observed in the perilesional skin. This study indicates the distorted frequency and functionality of DCs in the immunopathogenesis of PV. Targeting these functional markers in the future may generate novel therapeutic options for better management of PV.
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Acknowledgments
We thank All India Institute of Medical Sciences, New Delhi, India, for providing the Intramural Research Grant (IRG) to carry out this work.
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This study received funding from the Indian Council of Medical Research (ICMR- 61/4/2018-BMS) (Project code I-1034).
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Das, D., Singh, A., Antil, P.S. et al. Distorted frequency of dendritic cells and their associated stimulatory and inhibitory markers augment the pathogenesis of pemphigus vulgaris. Immunol Res 68, 353–362 (2020). https://doi.org/10.1007/s12026-020-09166-0
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DOI: https://doi.org/10.1007/s12026-020-09166-0