Differential Effects of Polymorphisms in the 5′ Flanking Region of<i>IL12RB2</i>on NK- and T-Cell Activity

Ohyama, Hideki; Kato-Kogoe, Nahoko; Nishimura, Fusanori; Takeuchi-Hatanaka, Kazu; Matsushita, Sho; Yamanegi, Koji; Yamada, Naoko; Hara, Masaki; Nakasho, Keiji; Terada, Nobuyuki

doi:10.1089/jir.2008.0133

Cited by 10 publications

(5 citation statements)

References 22 publications

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“…Expression of IL-12Rb2 is greater in tuberculoid lesions than in lepromatous lesions, whereas the expression of IL-12Rb1 is similar in both [Kim et al, 2001]. It is believed that susceptibility to various diseases related to mycobacterial pathogens could be determined by the degree of expression of IL-12Rb2, which can be regulated by genetic factors, including polymorphism IL12Rb2 [Ohyama et al, 2005[Ohyama et al, , 2008. The reported lack of expression of IL12Rb1 caused by mutations in the human gene, resulting in immunodeficiency with infections by Mycobacteria species as predominant disease, demonstrates the essential role of IL-12 in resistance to infections caused by intracellular parasite [Altare et al, 2001;de Jong et al, 1998].…”

Section: Genetic Influence Of Disease Outcome In Leprosymentioning

confidence: 99%

Clinical, immunological, and genetic aspects in leprosy

Simon

Scherlock

Duthie

et al. 2011

Drug Development Research

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Leprosy is a chronic infection caused by Mycobacterium leprae. It affects the skin and peripheral nerves and can cause irreversible chronic disabilities. The worldwide registered number of cases in 2009 was 213,036. This review discusses clinical aspects of the disease, including leprosy reactions and neuronal damage, as well as immunological and immunogenetic aspects influencing disease susceptibility and outcome. The cardinal signs of leprosy are skin lesions with altered sensation, thickened peripheral nerves, and presence of alcohol acid-resistant bacilli in skin biopsy or lymph. Confirmatory examinations include (1) bacteriological examination, which allows patients' classification into two operational groups, multibacillary (MB) and paucibacillary (PB); and (2) histopathological examination, which permits stratification in different clinical forms. These clinical forms differ not only by histopathology but also according to the host's immune response to M. leprae. These forms comprise the extremes of (1) tuberculoid leprosy (TT), with a specific Th1 response and control of M. leprae multiplication; (2) lepromatous leprosy (LL) without Th1 response and preserved Th2 response; and (3) the interpolar clinical forms, borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), and indeterminate form (IL). Appropriate treatment is based on smear examination or the number of lesions at diagnosis. In the evolution of leprosy, acute inflammation, known as reactions, may occur during or after treatment. These reactions are classified into two main types: the type I reaction or reversal reaction (RR), and the type II reaction or erythema nodosum leprosum (ENL). The role of innate immune response to control the infection is supported by immunological and genetic studies. Drug Dev Res 72:509-527, 2011.

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Section: Genetic Influence Of Disease Outcome In Leprosymentioning

confidence: 99%

Clinical, immunological, and genetic aspects in leprosy

Simon

Scherlock

Duthie

et al. 2011

Drug Development Research

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“…Two DE genes relating to the interleukin signalling pathway were present, and these were interleukin 12 receptor beta 2 ( IL12Rβ2 ), which was downregulated in the KO-MAP, and IL6 , which was upregulated. The IL12R is involved in the activation of T cells and natural killer (NK) cells [ 56 ]. Collectively, these findings indicate that upon MAP infection, IL10Rα knockout cells do still respond to MAP infection, however, the response is far less than what it would be in unedited cells.…”

Section: Discussionmentioning

confidence: 99%

The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

Fong,

Rochus,

Shandilya

et al. 2024

BMC Genom Data

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Background Johne’s disease is a chronic wasting disease caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Johne’s disease is highly contagious and MAP infection in dairy cattle can eventually lead to death. With no available treatment for Johne’s disease, genetic selection and improvements in management practices could help reduce its prevalence. In a previous study, the gene coding interleukin-10 receptor subunit alpha (IL10Rα) was associated with Johne’s disease in dairy cattle. Our objective was to determine how IL10Rα affects the pathogenesis of MAP by examining the effect of a live MAP challenge on a mammary epithelial cell line (MAC-T) that had IL10Rα knocked out using CRISPR/cas9. The wild type and the IL10Rα knockout MAC-T cell lines were exposed to live MAP bacteria for 72 h. Thereafter, mRNA was extracted from infected and uninfected cells. Differentially expressed genes were compared between the wild type and the IL10Rα knockout cell lines. Gene ontology was performed based on the differentially expressed genes to determine which biological pathways were involved. Results Immune system processes pathways were targeted to determine the effect of IL10Rα on the response to MAP infection. There was a difference in immune response between the wild type and IL10Rα knockout MAC-T cell lines, and less difference in immune response between infected and not infected IL10Rα knockout MAC-T cells, indicating IL10Rα plays an important role in the progression of MAP infection. Additionally, these comparisons allowed us to identify other genes involved in inflammation-mediated chemokine and cytokine signalling, interleukin signalling and toll-like receptor pathways. Conclusions Identifying differentially expressed genes in wild type and ILR10α knockout MAC-T cells infected with live MAP bacteria provided further evidence that IL10Rα contributes to mounting an immune response to MAP infection and allowed us to identify additional potential candidate genes involved in this process. We found there was a complex immune response during MAP infection that is controlled by many genes.

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“…However, in Korean patients, Lee et al [59] found no significant differences in allele frequencies of IL12RB1 between leprosy patients and the control group [59]. Now, in relation to gene in the 5′ flanking region of IL12RB2 , Ohyama et al [60] determined the functional effects of these SNPs on NK-cell activity, including IFN- γ production and IL-12RB2 gene expression. The results suggest that these SNPs in IL12RB2 have differential effects on cellular activation of T and NK cells [60].…”

Section: Cytokines and Leprosymentioning

confidence: 99%

“…Now, in relation to gene in the 5′ flanking region of IL12RB2 , Ohyama et al [60] determined the functional effects of these SNPs on NK-cell activity, including IFN- γ production and IL-12RB2 gene expression. The results suggest that these SNPs in IL12RB2 have differential effects on cellular activation of T and NK cells [60]. …”

Section: Cytokines and Leprosymentioning

confidence: 99%

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

Jarduli

Sell

Reis

et al. 2013

BioMed Research International

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Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.

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Differential Effects of Polymorphisms in the 5′ Flanking Region ofIL12RB2on NK- and T-Cell Activity

Cited by 10 publications

References 22 publications

Clinical, immunological, and genetic aspects in leprosy

Clinical, immunological, and genetic aspects in leprosy

The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

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