In situ T regulatory cells and Th17 cytokines in paired samples of leprosy type 1 and type 2 reactions

Abstract

Leprosy is a complex chronic, infectious dermato-neurological disease that affects the skin and peripheral nerves especially during immuno-inflammatory episodes known as type 1/T1R and type 2/T2R reactions. This study investigated the in situ expression of CD25+Foxp3+ Treg cells and TGF-β1, IFN-γ, IL-17 in leprosy T1R and T2R. Tregs were evaluated in 114 skin biopsies from 74 leprosy patients: 56 T1R (28-paired reaction-free/reactional biopsies, 28 unpaired T1R), 18 T2R (12 paired reaction-free/reactional biopsies, 6 unpaired T2R). Double CD25+Foxp3+immunostained Treg cells obtained by automated platform (Ventana BenchMark XT, Roche, Mannheim, Germany) were counted (Nikon Eclipse E400 2mm2). Cytokine expression was evaluated by immunostaining in 96 biopsies (48 paired reaction-free/reactional lesions, 24 T1R, 24 T2R) using rabbit polyclonal anti human TGF-β1, IFN-γ, IL-17 antibodies (Santa Cruz Biotechnology CA, USA). Treg cell counts in leprosy reactional lesions were higher compared to reaction-free (p = 0.002). Treg numbers were higher in T1R compared to paired unreactional T1R lesions (p = 0.001). Similar frequency of Treg was seen in paired reactional versus unreactional T2R lesions. Higher expression of TGF-β, IFN-γ and IL-17 was seen in T2R lesions compared to T1R and reaction-free lesions. The increase in Treg cells during T1R suggests a suppressive role to control the exacerbated cellular immune response during T1R that can cause tissue and nerve damage. Evidences of upregulated Treg cells in TR1, which usually occurs in patients with Th1-Th17 immunity and the indications of the expression of Th17/IL-17 in T2R, which develops in patients with Th2-Treg profile, suggest plasticity of Treg-Th17 cells populations and a potential role for these cell populations in the immunopathogenesis of leprosy reactions.

Advances in the Immunology and Genetics of Leprosy

“…Comparing to other forms of leprosy and healthy controls, T2R showed lowest circulating Treg frequency, which was consistent with the high Th17 frequency in T2R (58,76). But it is not the case for T1R, several studies have demonstrated that T1R showed a significantly higher frequency of Treg compared to nonreactional leprosy in both PBMC and skin lesions (58,74,(76)(77)(78). One possible explanation for the increase of Treg in T1R is that the increase of Treg in T1R is a self-protection mechanism to reduce the tissue damage caused by the exacerbated cell-mediated immune responses.…”

“…However, the reciprocal relationship between Treg and Th17 may be not applicable in leprosy reactions, especially for T1R. Since T1R and T2R are both acute inflammation reactions, it is reasonable to discover a higher frequency of Th17 in both T1R and T2R compared to non-reactional leprosy considering the inflammation functions of Th17 cells (73)(74)(75). Comparing to other forms of leprosy and healthy controls, T2R showed lowest circulating Treg frequency, which was consistent with the high Th17 frequency in T2R (58,76).…”

One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study

“…Proinflammatory cytokines, such as IL-17, are decisively involved in all clinical manifestations of SpA [9]. Th-17 responses include dysregulation of several IL-17 cytokines, and among these, IL-17A is crucial for the regulation of both innate and adaptive immune pathways [10].…”

Distribuição espacial da hanseníase infantil na região de Carajás-Pará

“…Outrossim, a inespecificidade na quantidade de casos com lesões cutâneas ignoradas é digno de atenção, levantando-se a hipótese de que diagnósticos podem estar sendo omitidos. Assim, quanto maior a quantidade de lesões maiores as chances de se tratar de uma forma multibacilar da hanseníase (SCHNEIDER; FREITAS, 2018), a qual está mais relacionada à transmissão da doença para outros indivíduos, por se tratar de uma forma em que há mais de 5 lesões (VIANA et al, 2017) e elas possuem maior carga bacteriana (COSTA et al, 2018). Desse modo, há enorme importância em se notificar a quantidade de lesões no controle do tratamento de hanseníase.…”