title: Distinctive Treg associated CCR4-CCL22 expression profile with altered frequency of Th17/Treg cell in the immunopathogenesis of Pemphigus Vulgaris.
abstract: Pemphigus Vulgaris (PV), a relatively common autoimmune blistering disease in India, primarily mediated by anti-Desmoglein 3 (anti-Dsg3) autoantibodies. T-helper 17 (Th17) and T-regulatory (Treg) cells play significant role in regulating immune homeostasis in autoimmune disorders. To understand immunopathogenesis of PV, it is crucial to unfold the phenotypic expression and functional characteristics of these cells along with their specific homing chemokine receptor-ligand. This proposed study aims to unravel the functional expression of Th17 and Treg cells along with their specific homing chemokine receptor-ligand, transcription factors and cytokine levels to better understand the immunopathogenesis of PV. The Flow cytometry results showed decreased frequency of Treg cells and high number of Th17 cells (p<0.001) indicating immune dysregulation in PV. A significant increase (p<0.001) in the serum levels of Th17 associated molecules (IL-17A, CCL-20) and relative expression of RORγt, CCR6 and CCL20 was found in patients. For Treg cells, transcription factor FOXp3 was significantly lowered along with defective CCR4-CCL22 (p<0.05) that might be playing an ambiguous role in Treg generated immune regulation, leading to homing defect at lesional sites. This maiden study revealed the role of defective receptor-ligand interface that might have failed to suppress inflammatory milieu produced by Th17 cells thus promoting inflammation and contributing to immunopathogenesis of PV. This chemokine receptor-ligand can further be explored as potential target for development of novel therapies in PV.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: R
authors.initials: R
authors.lastname: Asothai
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Anand
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Dayasagar
authors.initials: D
authors.lastname: Das
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Parul Singh
authors.initials: PS
authors.lastname: Antil
authors.affiliation: Department of Dermatology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sujay
authors.initials: S
authors.lastname: Khandpur
authors.affiliation: Department of Dermatology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: V K
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: dralpanasharma@gmail.com.
authors.forename: Alpana
authors.initials: A
authors.lastname: Sharma
mesh_terms: D054418:Chemokine CCL20 / Q000276:immunology; D054422:Chemokine CCL22 / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology; D054398:Receptors, CCR4 / Q000276:immunology*; D054399:Receptors, CCR6 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C108355:CCL20 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054422:Chemokine CCL22; C508717:IL17A protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D054398:Receptors, CCR4; D054399:Receptors, CCR6
keywords: CCR4-CCL22); Chemokine receptor-ligand (CCR6-CCL20; Foxp3; Pemphigus Vulgaris (PV); Rorγt; Th17/treg cells