Literature DB >> 22527432

Lessons of leprosy: the emergence of TH17 cytokines during type II reactions (ENL) is teaching us about T-cell plasticity.

Frank Martiniuk1, Jerome Giovinazzo, Ainah U Tan, Rozana Shahidullah, Patrick Haslett, Gilla Kaplan, William R Levis.   

Abstract

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.

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Year:  2012        PMID: 22527432      PMCID: PMC3412264     

Source DB:  PubMed          Journal:  J Drugs Dermatol        ISSN: 1545-9616            Impact factor:   2.114


  30 in total

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2.  Thalidomide increases the synthesis of IL-2 in cultures of human mononuclear cells stimulated with Concanavalin-A, Staphylococcal enterotoxin A, and purified protein derivative.

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Journal:  Immunity       Date:  2000-11       Impact factor: 31.745

5.  Pharmacogenetic associations of CYP2C19 genotype with in vivo metabolisms and pharmacological effects of thalidomide.

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Journal:  Cancer Biol Ther       Date:  2002 Nov-Dec       Impact factor: 4.742

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Journal:  J Immunol       Date:  1986-04-01       Impact factor: 5.422

8.  Thalidomide metabolism by the CYP2C subfamily.

Authors:  Yuichi Ando; Eiichi Fuse; William D Figg
Journal:  Clin Cancer Res       Date:  2002-06       Impact factor: 12.531

9.  Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.

Authors:  P A Haslett; L G Corral; M Albert; G Kaplan
Journal:  J Exp Med       Date:  1998-06-01       Impact factor: 14.307

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  12 in total

1.  Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells.

Authors:  Ana Paula Vieira; Maria Ângela Bianconcini Trindade; Carla Pagliari; João Avancini; Neusa Yurico Sakai-Valente; Alberto José da Silva Duarte; Gil Benard
Journal:  Am J Trop Med Hyg       Date:  2016-02-22       Impact factor: 2.345

2.  Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

Authors:  Michelle de Campos Soriani Azevedo; Heloisa Marques; Larissa Sarri Binelli; Mariana Silva Vieira Malange; Amanda Carreira Devides; Eliane Aparecida Silva; Luciana Raquel Vincenzi Fachin; Cassio Cesar Ghidella; Cleverson Teixeira Soares; Gustavo Pompermaier Garlet; Patrícia Sammarco Rosa; Andrea de Farias Fernandes Belone; Ana Paula Favaro Trombone
Journal:  Med Microbiol Immunol       Date:  2017-09-05       Impact factor: 3.402

3.  Increased serum circulatory levels of interleukin 17F in type 1 reactions of leprosy.

Authors:  Sundeep Chaitanya; Mallika Lavania; Ravindra P Turankar; Samuel Raj Karri; U Sengupta
Journal:  J Clin Immunol       Date:  2012-07-31       Impact factor: 8.317

4.  Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.

Authors:  Veronica Schmitz; Rhana Berto da Silva Prata; Mayara Garcia de Mattos Barbosa; Mayara Abud Mendes; Sheila Santos Brandão; Thaís Porto Amadeu; Luciana Silva Rodrigues; Helen Ferreira; Fabrício da Mota Ramalho Costa; Jessica Brandão Dos Santos; Fabiana Dos Santos Pacheco; Alice de Miranda Machado; José Augusto da Costa Nery; Mariana de Andrea Hacker; Anna Maria Sales; Roberta Olmo Pinheiro; Euzenir Nunes Sarno
Journal:  PLoS Negl Trop Dis       Date:  2016-08-24

Review 5.  Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease.

Authors:  Jorge Rodrigues de Sousa; Mirian Nacagami Sotto; Juarez Antonio Simões Quaresma
Journal:  Front Immunol       Date:  2017-11-28       Impact factor: 7.561

Review 6.  A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum.

Authors:  Anastasia Polycarpou; Stephen L Walker; Diana N J Lockwood
Journal:  Front Immunol       Date:  2017-03-13       Impact factor: 7.561

7.  New Players in the Same Old Game: Disturbance of Group 2 Innate Lymphoid Cells in HIV-1 and Mycobacterium leprae Co-infected Patients.

Authors:  Pedro Henrique Papotto; Solange Maeda; Jane Tomimori; Marília Brasil Xavier; Luiz Vicente Rizzo; Esper Georges Kallas; Karina Inácio Carvalho
Journal:  PLoS Negl Trop Dis       Date:  2015-09-03

Review 8.  Inflammatory Mediators of Leprosy Reactional Episodes and Dental Infections: A Systematic Review.

Authors:  D C B Cortela; A L de Souza Junior; M C L Virmond; E Ignotti
Journal:  Mediators Inflamm       Date:  2015-08-03       Impact factor: 4.711

9.  CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, Non Th2 T cells in human leprosy.

Authors:  Chaman Saini; V Ramesh; Indira Nath
Journal:  PLoS Negl Trop Dis       Date:  2013-07-25

10.  The Effects of Prednisolone Treatment on Cytokine Expression in Patients with Erythema Nodosum Leprosum Reactions.

Authors:  Edessa Negera; Stephen L Walker; Kidist Bobosha; Yonas Bekele; Birtukan Endale; Azeb Tarekegn; Markos Abebe; Abraham Aseffa; Hazel M Dockrell; Diana N Lockwood
Journal:  Front Immunol       Date:  2018-02-09       Impact factor: 7.561

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