title: Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6.
abstract: BACKGROUND
  50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.
  
  
  RESULTS
  Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.
  
  
  CONCLUSIONS
  Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.
authors.affiliation: National Institute of Pathology (ICMR) Safdarjung Hospital Campus, New Delhi, India.
authors.forename: Chaman
authors.initials: C
authors.lastname: Saini
authors.affiliation: Government Autonomous Holkar Science College, Indore, India.
authors.forename: Anisuddin
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Department of Dermatology, Safdarjung Hospital New Delhi, India.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Ramesh
authors.affiliation: National Institute of Pathology (ICMR) Safdarjung Hospital Campus, New Delhi, India.
authors.forename: Indira
authors.initials: I
authors.lastname: Nath
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D001769:Blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism*; D007918:Leprosy / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D016212:Transforming Growth Factor beta