Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction

Protein arginine methyltransferase 5 (PRMT5) controls diverse cellular processes and is implicated in cancer development and progression. Here, we report an inverse correlation between PRMT5 function and antitumor immunity. PRMT5 expression was associated with an antitumor immune gene signature in human melanoma tissue. Reducing PRMT5 activity antagonized melanoma growth in immunocompetent but not immunocompromised mice. PRMT5 methylation of IFI16 [interferon-γ (IFN-γ)–inducible protein 16] or its murine homolog IFI204, which are components of the cGAS/STING (stimulator of IFN genes) pathway, attenuated cytosolic DNA–induced IFN and chemokine expression in melanoma cells. PRMT5 also inhibited transcription of the gene encoding NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5), a protein that promotes the expression of genes implicated in major histocompatibility complex class I (MHCI) antigen presentation. PRMT5 knockdown augmented IFN and chemokine production and increased MHCI abundance in melanoma. Increased expression of IFI204 and NLRC5 was associated with decreased melanoma growth in murine models, and increased expression of IFI16 and NLRC5 correlated with prolonged survival of patients with melanoma. Combination of pharmacological (GSK3326595) or genetic (shRNA) inhibition of PRMT5 with immune checkpoint therapy limited growth of murine melanoma tumors (B16F10 and YUMM1.7) and enhanced therapeutic efficacy, compared with the effect of either treatment alone. Overall, our findings provide a rationale to test PRMT5 inhibitors in immunotherapy-based clinical trials as a means to enhance an antitumor immune response.

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Perdarahan Saluran Cerna sebagai Manifestasi Tuberkulosis Intestinum pada Pasien Lepra dengan Reaksi Reversal dan Riwayat Terapi Steroid Jangka Panjang

Jurnal Penyakit Dalam Indonesia ◽

10.7454/jpdi.v3i1.7 ◽

2017 ◽

Vol 3 (1) ◽

pp. 47

Author(s):

Meutia Gebrina ◽

Saskia Aziza Nursyirwan ◽

Pradana Soewondo ◽

Achmad Fauzi ◽

Kaka Renaldi

Keyword(s):

Gastrointestinal Bleeding ◽

Intestinal Tuberculosis ◽

Signs And Symptoms ◽

Leprosy Patients ◽

History Of ◽

Reversal Reaction ◽

Unusual Symptoms

Tuberkulosis usus merupakan suatu kondisi yang cukup sulit ditegakkan diagnosisnya. Gejala penyakit ini tidak khas dan pemeriksaan penunjang yang dilakukan seringkali menunjukkan hasil negatif. Salah satu gejala yang tidak khas dari tuberkulosis usus adalah perdarahan saluran cerna, yang harus menjadi kewaspadaan praktisi klinis.Kata kunci: perdarahan saluran cerna, tuberkulosis Gastrointestinal Bleeding as a Manifestation of Intestinal Tuberculosis in Leprosy Patients with Reversal Reaction and History of Long-Term Steroid TherapyIntestinal tuberculosis is difficult to be diagnosed. Signs and symptoms usually are not specific, and the results of diagnostictools are frequently negative. One of the unusual symptoms of intestinal tuberculosis is gastrointestinal bleeding, whichshould increase the awareness of clinical practitioners.Keywords: gastrointestinal bleeding, tuberculosis

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Allele frequencies for an interferon-γ microsatellite in a population of Brazilian leprosy patients

European Journal of Immunogenetics ◽

10.1046/j.1365-2370.2003.00377.x ◽

2003 ◽

Vol 30 (2) ◽

pp. 149-151 ◽

Cited By ~ 11

Author(s):

M. P. Reynard ◽

D. Turner ◽

A. P. Junqueira-Kipnis ◽

M. Ramos de Souza ◽

C. Moreno ◽

...

Keyword(s):

Interferon Γ ◽

Allele Frequencies ◽

Leprosy Patients

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Effect of Thalidomide on the Expression of TNF-α m-RNA and Synthesis of TNF-α in Cells from Leprosy Patients with Reversal Reaction

Immunopharmacology and Immunotoxicology ◽

10.1080/08923970600928023 ◽

2006 ◽

Vol 28 (3) ◽

pp. 431-441 ◽

Cited By ~ 10

Author(s):

Azeb Tadesse ◽

Markos Abebe ◽

Elizabeth Bizuneh ◽

Wondwossen Mulugeta ◽

Abraham Aseffa ◽

...

Keyword(s):

Tnf Α ◽

Leprosy Patients ◽

Reversal Reaction ◽

In Cells

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Human peripheral blood DNAM-1neg NK cells are a terminally differentiated subset with limited effector functions

Blood Advances ◽

10.1182/bloodadvances.2018030676 ◽

2019 ◽

Vol 3 (11) ◽

pp. 1681-1694 ◽

Cited By ~ 8

Author(s):

Kimberley A. Stannard ◽

Sébastien Lemoine ◽

Nigel J. Waterhouse ◽

Frank Vari ◽

Lucienne Chatenoud ◽

...

Keyword(s):

Nk Cells ◽

Peripheral Blood ◽

Nk Cell ◽

Human Peripheral Blood ◽

Cell Subset ◽

B Cell Lymphoma ◽

Gene Signature ◽

Interferon Γ ◽

Specific Gene

Abstract Natural killer (NK) cells are a heterogeneous population of innate lymphocytes whose potent anticancer properties make them ideal candidates for cellular therapeutic application. However, our lack of understanding of the role of NK cell diversity in antitumor responses has hindered advances in this area. In this study, we describe a new CD56dim NK cell subset characterized by the lack of expression of DNAX accessory molecule-1 (DNAM-1). Compared with CD56bright and CD56dimDNAM-1pos NK cell subsets, CD56dimDNAM-1neg NK cells displayed reduced motility, poor proliferation, lower production of interferon-γ, and limited killing capacities. Soluble factors secreted by CD56dimDNAM-1neg NK cells impaired CD56dimDNAM-1pos NK cell–mediated killing, indicating a potential inhibitory role for the CD56dimDNAM-1neg NK cell subset. Transcriptome analysis revealed that CD56dimDNAM-1neg NK cells constitute a new mature NK cell subset with a specific gene signature. Upon in vitro cytokine stimulation, CD56dimDNAM-1neg NK cells were found to differentiate from CD56dimDNAM-1pos NK cells. Finally, we report a dysregulation of NK cell subsets in the blood of patients diagnosed with Hodgkin lymphoma and diffuse large B-cell lymphoma, characterized by decreased CD56dimDNAM-1pos/CD56dimDNAM-1neg NK cell ratios and reduced cytotoxic activity of CD56dimDNAM-1pos NK cells. Altogether, our data offer a better understanding of human peripheral blood NK cell populations and have important clinical implications for the design of NK cell–targeting therapies.

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