Document Detail


Lessons of leprosy: the emergence of TH17 cytokines during type II reactions (ENL) is teaching us about T-cell plasticity.
MedLine Citation:
PMID:  22527432     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Leprosy was the first disease classified according to the thymus derived T-cell in the 1960s and the first disease classified by the cytokine profile as intact interferon-γ (IFN-γ) and interleukin-2 (IL2) or TH1 (tuberculoid) and deficient IFN-γ and IL2 or TH2 (lepromatous), in the 1980s. Objective: In the present study, we set out to explore the T helper 17 (TH17) lymphocyte subset, the hallmark of T-cell plasticity, in skin biopsies from patients with erythema nodosum leprosum (ENL) who were treated with thalidomide.
METHOD: RNA was extracted from paraffin embedded tissue before and after thalidomide treatment of ENL and RT-PCR was performed.
RESULTS: IL17A, the hallmark of TH17, was consistently seen before and after thalidomide treatment, confirming the TH17 subset to be involved in ENL and potentially up-regulated by thalidomide.
CONCLUSION: A reduction in CD70, GARP, IDO, IL17B (IL-20), and IL17E (IL-25), coupled with increases in RORγT, ARNT, FoxP3, and IL17C (IL-21) following thalidomide treatment, opens the door to understanding the complexity of the immunomodulatory drug thalidomide, which can operate as an anti-inflammatory while simultaneously stimulating cell-mediated immunity (CMI). We conclude that TH17 is involved in the immunopathogenesis of ENL and that thalidomide suppresses inflammatory components of TH17, while enhancing other components of TH17 that are potentially involved in CMI.
Authors:
Frank Martiniuk; Jerome Giovinazzo; Ainah U Tan; Rozana Shahidullah; Patrick Haslett; Gilla Kaplan; William R Levis
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of drugs in dermatology : JDD     Volume:  11     ISSN:  1545-9616     ISO Abbreviation:  J Drugs Dermatol     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-24     Completed Date:  2012-08-15     Revised Date:  2013-02-28    
Medline Journal Info:
Nlm Unique ID:  101160020     Medline TA:  J Drugs Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  626-30     Citation Subset:  IM    
Affiliation:
Pulmonary Division, New York University Department of Medicine, New York, NY, USA. martif02@nyumc.org
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Biopsy
Cytokines / immunology
Erythema Nodosum / drug therapy,  immunology*
Gene Expression Regulation / drug effects
Humans
Interleukin-17 / genetics,  immunology
Leprostatic Agents / pharmacology,  therapeutic use
Leprosy, Lepromatous / drug therapy,  immunology*
Male
Middle Aged
RNA / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Th17 Cells / immunology*
Thalidomide / pharmacology,  therapeutic use*
Up-Regulation / drug effects
Young Adult
Grant Support
ID/Acronym/Agency:
1UL1RR029893/RR/NCRR NIH HHS; UL1 RR029893/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-17; 0/Leprostatic Agents; 50-35-1/Thalidomide; 63231-63-0/RNA
Comments/Corrections

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