Distorted frequency of dendritic cells and their associated stimulatory and inhibitory markers augment the pathogenesis
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ORIGINAL ARTICLE
Distorted frequency of dendritic cells and their associated stimulatory and inhibitory markers augment the pathogenesis of pemphigus vulgaris Dayasagar Das 1 & Ashu Singh 1 & Parul Singh Antil 1 & Divya Sharma 1 & Sudheer Arava 2 & Sujay Khandpur 3 & Alpana Sharma 1 Received: 14 December 2019 / Accepted: 31 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 patientderived 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. Keywords Pemphigus vulgaris . Dendritic cells . Co-stimulatory markers (CD40, CD80) . Inhibitory markers (ILT3, PSGL1)
Introduction Pemphigus vulgaris (PV) is a classical example of antigendriven mucocutaneous blistering disease. It is exemplified by intra-epidermal blisters and immunopathologically by circulating autoantibody directed against desmoglein protein at the surface of keratinocyte [1, 2]. The precise triggering factors for PV and other autoimmune diseases are largely * Alpana Sharma [email protected] 1
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
2
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3
Department of Dermatology & Venereology, All India Institute of Medical Sciences, New Delhi, India
unknown. The probable causes for triggering PV comprise multiple factors including the aberrant function of T helper 17(Th17), T regulatory cells (Treg), and their associated chemokine receptor-ligand [3, 4]. Besides, the key initial step in
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