Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Hervier, B.; Perez, Mikael; Allenbach, Yves; Devilliers, H.; Cohen, Fleur; Uzunhan, Y.; Ouakrim, Hanane; Dorgham, Karim; Méritet, Jean–François; Longchampt, Élisabeth; Stenzel, Werner; Cremer, Isabelle; Benveniste, Olivier; Vieillard, Vincent

doi:10.4049/jimmunol.1501902

Cited by 31 publications

(34 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to type II IFN signature, we observed CD8+ T cells in close vicinity of MHC-2 expressing myofibres in both ASM and IBM (figure 3). NK cells are rare in muscular inflammatory infiltrates in ASM21 and virtually absent in IBM 22. This finding points out CD8+ T cells as a likely source of local IFNγ production in ASM and IBM.…”

Section: Discussionmentioning

confidence: 61%

Distinct interferon signatures stratify inflammatory and dysimmune myopathies

et al. 2019

View full text Add to dashboard Cite

ObjectiveThe role of interferons (IFN) in the pathophysiology of primary inflammatory and dysimmune myopathies (IDM) is increasingly investigated, notably because specific neutralisation approaches may constitute promising therapeutic tracks. In present work we analysed the muscular expression of specific IFNα/β and IFNγ-stimulated genes in patients with various types of IDM.Methods39 patients with IDM with inclusion body myositis (IBM, n=9), dermatomyositis (DM, n=10), necrotising autoimmune myopathies (NAM, n=10) and antisynthetase myositis (ASM, n=10), and 10 controls were included. Quantification of expression levels of IFNγ, ISG15, an IFNα/β-inducible gene and of six IFNγ-inducible genes (GBP2, HLA-DOB, HLA-DPB, CIITA, HLA-DRB and HLA-DMB) was performed on muscle biopsy samples.ResultsDM usually associated with strong type I IFNα/β signature, IBM and ASM with prominent type II IFNγ signature and NAM with neither type I nor type II IFN signature. Immunofluorescence study in ASM and IBM showed myofibre expression of major histocompatibility class 2 (MHC-2) and CIITA, confirming the induction of the IFNγ pathway. Furthermore, MHC-2-positive myofibres were observed in close proximity to CD8+ T cells which produce high levels of IFNγ.ConclusionDistinct IFN signatures allow a more distinct segregation of IDMs and myofibre MHC-2 expression is a reliable biomarker of type II IFN signature.

show abstract

Section: Discussionmentioning

confidence: 61%

Distinct interferon signatures stratify inflammatory and dysimmune myopathies

et al. 2019

View full text Add to dashboard Cite

show abstract

“…As we rapidly observed that NK cells belonging to this cohort presented immune abnormalities, we decided to introduce and use control samples belonging to a pool of over 250 anonymous individuals from the French National Blood Bank (EFS, Paris, France), called EFS-Ctl, currently used as the standard for the routine biological diagnosis of NK lymphoproliferative diseases (i.e., LGL, leukemia, etc.) and for other related immune disorders in the Department of Immunology of the Pitié-Salpêtrière hospital as previously described [32–34]. These blood samples were certified for their absence of common viral infections (i.e., HIV-1 and 2, hepatitis B and C viruses) and lymphocyte dysfunction (absolute value and frequency of subpopulation, activation status) (https://www.legifrance.gouv.fr/eli/arrete/2016/4/5/AFSP1608360A/jo/texte).…”

Section: Methodsmentioning

confidence: 99%

Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events?

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background Autism spectrum disorders (ASD) are characterized by abnormal neurodevelopment, genetic, and environmental risk factors, as well as immune dysfunctions. Several lines of evidence suggest alterations in innate immune responses in children with ASD. To address this question in adults with high-functioning ASD (hf-ASD), we sought to investigate the role of natural killer (NK) cells in the persistence of ASD. Methods NK cells from 35 adults with hf-ASD were compared to that of 35 healthy controls (HC), selected for the absence of any immune dysfunctions, at different time-points, and over a 2-year follow-up period for four patients. The phenotype and polyfunctional capacities of NK cells were explored according to infectious stigma and clinical parameters (IQ, social, and communication scores). Results As compared to HC, NK cells from patients with hf-ASD showed a high level of cell activation ( p < 0.0001), spontaneous degranulation ( p < 0.0001), and interferon-gamma production ( p = 0.0004), whereas they were exhausted after in vitro stimulations ( p = 0.0006). These data yielded a specific HLA-DR + KIR2DL1 + NKG2C + NK-cell signature. Significant overexpression of NKG2C in hf-ASD patients ( p = 0.0005), indicative of viral infections, was inversely correlated with the NKp46 receptor level ( r = − 0.67; p < 0.0001), regardless of the IgG status of tested pathogens. Multivariate linear regression analysis also revealed that expression of the late-activating HLA-DR marker was both associated with structural language ( r = 0.48; p = 0.007) and social awareness ( r = 0.60; p = 0.0007) scores in adult patients with hf-ASD, while KIR2DL1 expression correlated with IQ scores ( p = 0.0083). Conclusions This study demonstrates that adults with hf-ASD have specific NK-cell profile. Presence of NKG2C overexpression together with high-level activation of NK cells suggest an association with underlying pathogens, a hypothesis warranting further exploration in future studies. Electronic supplementary material The online version of this article (10.1186/s13229-019-0269-1) contains supplementary material, which is available to authorized users.

show abstract

“…Acted as chemoattractants for leukocytes The unique N-terminal extension domain of AsnRS was associated with the CCR3-mediated chemotactic activity 72,73 HisRS Provoked myositis in mice By MyD88-dependent TLRs 74 ARSs served as autoantigens in ASSD patients NK cells might contribute to the development of ASSD NK cells had abnormal phenotypic characterization and function 75 HisRS in polymyositis patients PBMC-derived APCs and DCs mediated peripheral blood T cell proliferation triggered by HisRS The Shiga toxins induced KRS secretion from macrophage-like differentiated THP-1. In turn, the secreted KRS promoted the production of pro-inflammatory cytokines in THP-1 cells 106 Tumor immunity ThrRS Manipulated the tumor microenvironment through regulating angiogenesis and immune cell responses ThrRS levels were correlated with VEGF, and it was over-expressed in infiltrating leukocytes 108…”

Section: Referencesmentioning

confidence: 99%

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Nie

Sun

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Aminoacyl-tRNA synthetases (ARSs) play a vital role in protein synthesis by linking amino acids to their cognate transfer RNAs (tRNAs). This typical function has been well recognized over the past few decades. However, accumulating evidence reveals that ARSs are involved in a wide range of physiological and pathological processes apart from translation. Strikingly, certain ARSs are closely related to different types of immune responses. In this review, we address the infection and immune responses induced by pathogen ARSs, as well as the potential anti-infective compounds that target pathogen ARSs. Meanwhile, we describe the functional mechanisms of ARSs in the development of immune cells. In addition, we focus on the roles of ARSs in certain immune diseases, such as autoimmune diseases, infectious diseases, and tumor immunity. Although our knowledge of ARSs in the immunological context is still in its infancy, research in this field may provide new ideas for the treatment of immune-related diseases.

show abstract

Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Cited by 31 publications

References 37 publications

Distinct interferon signatures stratify inflammatory and dysimmune myopathies

Distinct interferon signatures stratify inflammatory and dysimmune myopathies

Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events?

Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases

Contact Info

Product

Resources

About