The WAP protein Trappin-2/Elafin: A handyman in the regulation of inflammatory and immune responses

Verrier, Thomas; Solhonne, Brigitte; Sallenave, Jean–Michel; García-Verdugo, Ignacio

doi:10.1016/j.biocel.2012.05.007

Cited by 44 publications

(43 citation statements)

References 30 publications

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“…Severe disease subjects had higher expression levels of several cytokine and chemokine genes (IL-8, TNF), antiviral signaling genes including TMEM158 (or STING), an endoplasmic reticulum adaptor protein that plays a pivotal role in antiviral immune signaling (13), and CD69, a C-type lectin that is involved in T cell activation, proliferation, and signaling (23). In addition to higher expression of pro-inflammatory genes, subjects with history of severe infection also showed higher levels of anti-inflammatory genes such as PI3, a protease inhibitor that acts to reduce inflammation (37), and TNFAIP3, which inhibits NF-kappa B activation (33). Gene set enrichment analysis (GSEA) (34) identified several immune-related pathways that were differentially expressed between asymptomatic and severe subjects (FDR < 0.05).…”

Section: Differential Gene Expression Between Severe and Asymptomaticmentioning

confidence: 99%

Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus

Qian

Thakar²,

Yuan³

et al. 2014

Viral Immunology

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Infections with West Nile virus (WNV) are typically asymptomatic, but some patients experience severe neurological disease and even death. Over 1500 fatalities have resulted from the more than 37,000 WNV cases in the USA between 1999 and 2012. While it is clear that age is a significant risk factor, markers of immune status associated with susceptibility to severe infections are incompletely defined. We have taken advantage of stable characteristics of individual status to profile immune markers from a stratified cohort of healthy subjects with a history of asymptomatic or severe infection with WNV. We characterized individual variations in antibody and serum cytokine levels and genome-wide transcriptional profiles of peripheral blood cells (PBMCs). While antibody levels were not significantly different between cohorts, we found that subjects with a history of severe infection had significantly lower levels of serum IL-4, and that these changes in IL-4 levels were associated with altered gene expression patterns in PBMCs. In addition, we identified a signature of 105 genes that displayed altered expression levels when comparing subjects with a history of asymptomatic or severe infection. These results suggest that systems-level analysis of immune system status can be used to identify factors relevant for susceptibility to severe infections, and specifically point to an important contribution for IL-4 in resistance to WNV infection.

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Section: Differential Gene Expression Between Severe and Asymptomaticmentioning

confidence: 99%

Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus

Qian

Thakar²,

Yuan³

et al. 2014

Viral Immunology

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“…According to previous studies, subjects with severe infection exhibit high expression levels of cytokine and chemokine genes (IL-8, TNF), antiviral signaling genes such as TMEM158 (involved in antiviral immune signaling) (Ishikawa and Barber 2008), and CD69, a C-type lectin that plays a vital role in T cell activation, proliferation and signaling (Martín and Sán-chez-Madrid 2011). Moreover, it has been observed in subjects with history of severe infection displayed higher expression levels of anti-inflammatory proteins such as PI3, a protease inhibitor that acts to reduce inflammation (Verrier et al 2012), and TNFAIP3 that restrains NF-kappa B activation (Song et al 1996).…”

Section: Discussionmentioning

confidence: 98%

Identification of hub genes and their SNP analysis in West Nile virus infection for designing therapeutic methodologies using RNA-Seq data

et al. 2015

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The West Nile virus (WNV) infections are generally asymptomatic and are considered as immediate concerns of biodefense due to the lack of any therapeutic remedies. In this work, we created an interaction network of 1159 differentially expressed genes to detect potential hub genes from WNV infected primary human macrophages. We go on to explore the genetic variations that can alter the expression and function of identified hub genes (HCLS1, SLC15A3, HCK, and LY96) using the PROVEAN Protein Batch tool and PolyPhen-2. Community analysis of the network revealed that these clusters were enriched in GO terms such as inflammatory response and regulation of proliferation. Analysis of hub genes can aid in determining their degree of conservation and may help us in understanding their functional roles in biological systems. The nsSNPs proposed in this work may be further targeted through experimental methods for improving treatment towards the infection of WNV.

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“…The various mechanisms through which elafin acts on the cutaneous immune homeostasis make it a candidate effector molecule of interest in the pathogenesis of GVHD. Besides its major role as an inhibitor of neutrophil-derived elastases, elafin has antimicrobial, immunomodulatory, and tissueremodeling properties Verrier et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Although elafin is not detectable in normal skin, it is secreted abundantly in psoriasis and other inflammatory (Tanaka et al, 2000;Kamsteeg et al, 2010), as well as neoplastic (Alkemade et al, 1993), skin disorders. Elafin acts in various ways on the cutaneous immune homeostasis by not only exerting antiprotease effects but also immunomodulatory and antiproliferative ones Verrier et al, 2012). Hence, keratinocyte-derived elafin seems to favor the development of a T helper type1 response , but it can also enhance the resolution of inflammation by facilitating phagocytosis of apoptotic leukocytes .…”

Section: Introductionmentioning

confidence: 98%

Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease

Brüggen

Petzelbauer

Greinix

et al. 2015

Journal of Investigative Dermatology

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Graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. In the skin, GVHD can present in an acute (aGVHD), chronic lichenoid (clGVHD), or chronic sclerotic form (csGVHD). Measuring peripheral blood levels of the keratinocyte-derived protease inhibitor elafin has recently emerged as a promising tool for the diagnosis of cutaneous aGVHD. We evaluated whether the analysis of elafin expression in skin would allow distinguishing aGVHD from drug hypersensitivity rashes (DHR) and whether cutaneous elafin expression would correlate with disease severity or altered prognosis of aGVHD and clGVHD/csGVHD. Skin biopsies from aGVHD (n=22), clGVHD (n=15), csGVHD (n=7), and DHR (n=10) patients were collected and epidermal elafin expression and its association with diverse clinical/histological parameters were analyzed. Acute GVHD and DHR displayed varying degrees of elafin expression. No elafin was detectable in csGVHD, whereas the molecule was increased in clGVHD as compared with aGVHD. Elafin-high aGVHD/clGVHD lesions presented with epidermal thickening and were associated with poor prognosis-i.e., decreased overall survival in aGVHD and corticosteroid resistance in clGVHD. Although cutaneous elafin does not seem to discriminate aGVHD from DHR lesions, our study strongly suggests an association between cutaneous elafin expression and poor prognosis for patients with cutaneous GVHD.

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The WAP protein Trappin-2/Elafin: A handyman in the regulation of inflammatory and immune responses

Cited by 44 publications

References 30 publications

Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus

Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus

Identification of hub genes and their SNP analysis in West Nile virus infection for designing therapeutic methodologies using RNA-Seq data

Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease

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