Decreased RNA expression of interleukin 17A in skin of leprosy

Motta-Passos, Isabella da; Malheiro, Adriana; Naveca, Felipe Gomes; Passos, Luiz Fernando de Souza; Cardoso, Cristina Ribeiro de Barros; Cunha, Maria da Graça Souza; Santos, M.P.; Silva, George Allan Villarouco; Fraporti, Liziara Silva; Paula, Leandro Raphael N. de.

doi:10.1684/ejd.2012.1741

Cited by 11 publications

(5 citation statements)

References 41 publications

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“…As already said, although not associated with leprosy in our case-control study, the rs4833095 is a non-synonymous coding SNP so these results indicate that this marker might have a regulatory role in the production of these molecules under M. leprae infection. Regarding IL-17 in leprosy, results are contradictory, with some studies indicating poor production in serum and low expression in situ, whereas other studies have shown an increased expression in leprosy lesions (da Motta-Passos et al 2012, Trombone et al 2012). In our cohort, leprosy patients’s serum produced higher IL-17 concentrations as compared to health controls (p < 0.05, data nor shown).…”

Section: Discussionmentioning

confidence: 98%

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

Santana

Rêgo

Oliveira

et al. 2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations.OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy.METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions.FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes.MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease.

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Section: Discussionmentioning

confidence: 98%

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

Santana

Rêgo

Oliveira

et al. 2017

Mem. Inst. Oswaldo Cruz

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“…The differences between our and their findings may be related to differences between the two ethnically diverse populations. That Candida albicans and Staphylococcus aureus induce Th17 cells that produce different cytokines such as IFN-γ or IL-10 in addition to IL-17 would suggest that regulation of these cells is not only pathogen dependant but also due to other factors such as cytokines and transcription factors [48]. In human tuberculosis, predominance of IL-22 over IL-17 has been seen at the site of disease [49], a feature that was not observed in the skin lesions of leprosy.…”

Section: Discussionmentioning

confidence: 99%

CD4+ Th17 Cells Discriminate Clinical Types and Constitute a Third Subset of Non Th1, Non Th2 T Cells in Human Leprosy

2013

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BackgroundPatients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls.Methodology/Principle FindingsAn array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells.Conclusions/SignificanceIL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003). This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17+ cells. The Th17 cells were CD4+ CCR6+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01). Our study draws attention to a third type of effector Th cell that may play a role in leprosy.

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“…In BL, Th17 cells play a protective role in the immune response 13,22 secreting IFN-γ, IL-4 and IL-5 13 . Conflicting data concerning IL-17 levels have been reported, suggesting decreased levels in the serum of patients with leprosy 23,24 , whereas other studies 13,14,17,25 have reported higher levels in the TT/BT polar forms than in the LL form [11][12][13][14]25,26 . Furthermore, one study concerning IL-17F identified higher levels in non-reactional patients than in healthy controls, suggesting the greater the bacillary load, the greater the secretion of IL-17F 17 .…”

Section: Th17 Levels In the Clinical Forms Of Leprosymentioning

confidence: 96%

Th17 Cells and Cytokines in Leprosy: Understanding the Immune Response and Polarization

Zaniolo,

Damazo

2023

Rev. Soc. Bras. Med. Trop.

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While there are conflicting data concerning interleukin (IL)-17 levels in the serum of patients with leprosy compared with those in healthy controls, higher levels have been more evident in the tuberculoid clinical form of leprosy and type 1 reactions. This review aimed to highlight the role of Th17 cells and their cytokines in leprosy. Cytokines such as IL-1β and IL-23 induce Th17, while transforming growth factor beta and IL-10 inhibit Th17, indicating that the balance between Th17 and regulatory T cells is crucial for leprosy polarization. However, more comprehensive paired studies are required to better elucidate the role of Th17 cells in leprosy.

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Decreased RNA expression of interleukin 17A in skin of leprosy

Cited by 11 publications

References 41 publications

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

CD4+ Th17 Cells Discriminate Clinical Types and Constitute a Third Subset of Non Th1, Non Th2 T Cells in Human Leprosy

Th17 Cells and Cytokines in Leprosy: Understanding the Immune Response and Polarization

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