Disequilibrium of Tregs and TH17 cells in the pathogenesis of autoimmune skin disorder: Pemphigus vulgaris
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1
All India Institute of Medical Sciences (AIIMS), Department of Biochemistry,, India
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2
All India Institute of Medical Sciences (AIIMS), Department of Dermatology, India
Background: Pemphigus vulgaris (PV) is an auto-immune blistering disease forming auto-antibodies against desmoglein 3 (Dsg3). Treg and TH17 cells play important role in autoimmune diseases. Reason of paucity of Treg cells in PV lesions and Involvement of homing receptor and its ligand needs to be explored. We aim to assess the frequency of Treg and TH17 cells and quantitative expression of their cytokines, transcription factors, chemokine receptor-ligands in PV.
Methodology: 25 active PV patients (confirmed by clinical, histological diagnosis and anti-Dsg3 levels), 15 controls (non-inflammatory lypoma patients) were included. Serum TGF-β, IL-17, CCL20 and CCL22 levels were analysed by ELISA. Molecular expression of Foxp3, CCR4, CCL22 and RORγt, CCR6, CCL20 was performed by Real time PCR. Frequency of Treg and TH17 cells was assessed by Flow cytometry.
Results: Frequency of TH17 cells was significantly higher than Treg cells (p<0.02, p<0.008) in circulation of PV patients vs controls. For Tregs, levels of TGF-β were significantly elevated whereas CCL22 lowered in patients. Foxp3 expression was higher in tissues whereas relative expression of CCR4 was significantly lower in both blood and tissue (p<0.05) of patients. For TH17, significantly elevated level of IL-17 was found in patients. Relative expression of RORγt, CCR6 and CCL20 was significantly high in both blood and tissue of patients (p<0.001) as compared to controls.
Conclusion: Augmented expression of RORγt, CCR6, CCL20, Foxp3, CCL22 and lower expression of CCR4 in tissue signifies chemokine receptor-ligand imbalance of Treg cells that might affect the suppressive ability of iTregs over TH17 in pathogenesis of PV.
Keywords:
Th17,
Treg,
Pemphigus Vulgaris,
Autoimmune disorder,
RORγt,
Chemokine receptors
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Sharma
A,
R
A,
Anand
V and
Khandpur
S
(2013). Disequilibrium of Tregs and TH17 cells in the pathogenesis of autoimmune skin disorder: Pemphigus vulgaris.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00886
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Received:
21 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Alpana Sharma, All India Institute of Medical Sciences (AIIMS), Department of Biochemistry,, New delhi, 110029, India, dralpanasharma@gmail.com