scholarly journals Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status

BMC Genetics ◽  
2010 ◽  
Vol 11 (1) ◽  
pp. 23 ◽  
Author(s):  
Chris P Verschoor ◽  
Sameer D Pant ◽  
Qiumei You ◽  
Flavio S Schenkel ◽  
David F Kelton ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Interleukin 10 ◽  
Infection Status ◽  
Gene Encoding ◽  
Receptor Alpha

scholarly journals Functional analysis of bovine interleukin-10 receptor alpha in response to Mycobacterium avium subsp. paratuberculosis lysate using CRISPR/Cas9

BMC Genetics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanjay Mallikarjunappa ◽  
Umesh K. Shandilya ◽  
Ankita Sharma ◽  
Kristen Lamers ◽  
Nathalie Bissonnette ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Inflammatory Cytokine ◽  
Interleukin 10 ◽  
Negative Regulator ◽  
Cytokine Gene Expression ◽  
Economic Losses ◽  
Cytokine Signaling ◽  
Knock Out ◽  
Receptor Alpha ◽  
Anti Inflammatory

Abstract Background The interleukin-10 receptor alpha (IL10RA) gene codes for the alpha chain of the IL-10 receptor which binds the cytokine IL-10. IL-10 is an anti-inflammatory cytokine with immunoregulatory function during the pathogenesis of many inflammatory disorders in livestock, including Johne’s disease (JD). JD is a chronic enteritis in cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is responsible for significant economic losses to the dairy industry. Several candidate genes including IL10RA have been found to be associated with JD. The aim of this study was to better understand the functional significance of IL10RA in the context of immune stimulation with MAP cell wall lysate. Results An IL10RA knock out (KO) bovine mammary epithelial cell (MAC-T) line was generated using the CRISPR/cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) gene editing system. These IL10RA KO cells were stimulated with the immune stimulant MAP lysate +/− IL-10, or with LPS as a positive control. In comparison to unedited cells, relative quantification of immune-related genes after stimulation revealed that knocking out IL10RA resulted in upregulation of pro-inflammatory cytokine gene expression (TNFA, IL1A, IL1B and IL6) and downregulation of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of pro-inflammatory cytokine signaling. At the protein level knocking out IL10RA also resulted in upregulation of inflammatory cytokines - TNF-α and IL-6 and chemokines - IL-8, CCL2 and CCL4, relative to unedited cells. Conclusions The findings of this study illustrate the broad and significant effects of knocking out the IL10RA gene in enhancing pro-inflammatory cytokine expression and further support the immunoregulatory role of IL10RA in eliciting an anti-inflammatory response as well as its potential functional involvement during the immune response associated with JD.

scholarly journals Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium avium subsp. paratuberculosis in Monocyte-Derived Macrophages from Naturally Infected Cattle

2004 ◽  
Vol 72 (4) ◽  
pp. 1974-1982 ◽  
Author(s):  
M. S. Khalifeh ◽  
J. R. Stabel
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Mycobacterium Avium ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT Gamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. avium subsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

scholarly journals ICOSLG-mediated regulatory T cell expansion and IL-10 production promote progression of glioblastoma

2019 ◽  
Author(s):  
Ryoichi Iwata ◽  
Joo Hyoung Lee ◽  
Mikio Hayashi ◽  
Umberto Dianzani ◽  
Kohei Ofune ◽  
...  
Keyword(s):  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 10 ◽  
Dependent Manner ◽  
Gene Encoding ◽  
Checkpoint Proteins ◽  
Underlying Mechanisms ◽  
Immune Checkpoint Proteins ◽  
Factor Α ◽  
Regulatory Ligands

Abstract Background Targeting immune checkpoint proteins has recently gained substantial attention due to the dramatic success of this strategy in clinical trials for some cancers. Inducible T-cell co-stimulator ligand (ICOSLG) is a member of the B7 family of immune regulatory ligands, expression of which in cancer is implicated in disease progression due to regulation of anti-tumor adaptive immunity. Although aberrant ICOSLG expression has been reported in glioma cells, the underlying mechanisms that promote glioblastoma (GBM) progression remain elusive. Methods Here, we investigated a causal role for ICOSLG in GBM progression by analyzing ICOSLG expression in both human glioma tissues and patient-derived GBM sphere cells (GSCs). We further examined its immune modulatory effects and the underlying molecular mechanisms. Results Bioinformatics analysis and GBM tissue microarray showed that upregulation of ICOSLG expression was associated with poor prognosis in patients with GBM. ICOSLG expression was upregulated preferentially in mesenchymal GSCs but not in proneural GSCs in a tumor necrosis factor-α-/NF-ĸB-dependent manner. Furthermore, ICOSLG expression by mesenchymal GSCs promoted expansion of T cells that produced interleukin-10. Knockdown of the gene encoding ICOSLG markedly reduced GBM tumor growth in immune competent mice, with a concomitant downregulation of interleukin-10 levels in the tumor microenvironment. Conclusions Inhibition of the ICOSLG-ICOS axis in GBM may provide a promising immunotherapeutic approach for suppressing a subset of GBM with an elevated mesenchymal signature.

scholarly journals Mycobacterium avium paratuberculosis infection of calves – The impact of dam infection status

2020 ◽  
Vol 181 ◽  
pp. 104634 ◽  
Author(s):  
S. Patterson ◽  
K. Bond ◽  
M. Green ◽  
S. van Winden ◽  
J. Guitian
Keyword(s):  
Mycobacterium Avium ◽  
Infection Status ◽  
Mycobacterium Avium Paratuberculosis ◽  
The Impact

scholarly journals The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor

1998 ◽  
Vol 187 (4) ◽  
pp. 571-578 ◽  
Author(s):  
Susan D. Spencer ◽  
Francesco Di Marco ◽  
Jeff Hooley ◽  
Sharon Pitts-Meek ◽  
Michele Bauer ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Mutant Mice ◽  
Chromosome 21 ◽  
Orphan Receptor ◽  
Type I ◽  
Gene Encoding ◽  
Mediated Effects ◽  
A Subunit ◽  
Essential Subunit

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By ∼12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10–deficient mice. These findings suggest that CRF2-4 is essential for IL-10–mediated effects and is a subunit of the IL-10 receptor.

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