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

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.

Conflict of interest statement

Authors have no conflict of interest or disclosures to declare

Figures

Figure 1

Composite photograph of agarose gel electrophoresis of representative PCR amplicons for genes indicated pre- and post thalidomide treatment for Nepal ENL patients. HGAPDH and 100 bp DNA ladder are in the left three lanes. In A are genes with decreased expression after thalidomide treatment. In B are genes with increased expression after thalidomide treatment.