Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus

Deng, Yu; Huang, Zhizhou; Zhou, Cunjian; Wang, J.W.; You, Yi; Song, Zhiqiang; Xiang, Mingming; Zhong, B-Y; Fei, Hao

doi:10.1016/j.molimm.2005.07.039

Cited by 41 publications

(28 citation statements)

References 56 publications

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“…10 Additionally, TRIM22 has been implicated in normal hematopoietic differentiation and in diseases such as systemic lupus erythematosus and Wilms tumor. [17][18][19] In the present study we found that TRIM22 was one of the most strongly induced TRIM family molecules in human hepatoma HepG2 cells after treatment with IFNs, which have been demonstrated to be able to inhibit HBV replication noncytopathically. 20 Chisari and colleagues 21 also reported an association between TRIM22 and HBV clearance by microarray analysis in acutely HBV-infected chimpanzees.…”

supporting

confidence: 53%

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

et al. 2009

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Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. W ith over 300 million carriers, hepatitis B virus (HBV) infection remains a major public health problem worldwide. 1 Classified in the Hepadnaviridae family, HBV is a small, enveloped DNA virus with a genome size of 3.2 kb. HBV replicates its partially double-stranded DNA genome within core particles by reverse transcription of encapsulated 3.5-kb pregenomic RNA (pgRNA), and thus is related to retroviruses. 2 The core promoter (CP) is responsible for the synthesis of pgRNA, and therefore the regulation of this promoter is important in the viral life cycle. It is well established that resolution of HBV infection is critically dependent on adaptive immunity, especially on HBVspecific cytotoxic T lymphocytes response. However, many studies also indicate that an innate immune response is crucial for early clearance of HBV infection. 3 For example, activation of Toll-like receptor signaling can inhibit HBV replication in vivo, and overexpression of an innate antiviral molecule, APOBEC3G, has also been shown to interfere with HBV replication efficiently. 4,5 Recent studies show that many members of the tripartite motif (TRIM) superfamily are expressed in response to interferons (IFNs) and display antiviral properties, targeting retroviruses in particular. 6,7 TRIM5␣, TRIM19, TRIM22, and TRIM28 were all demonstrated to play important roles in antiretroviral activities. [8][9][10][11][12] It has been speculated that the TRIM proteins may represent a new and widespread class of antiviral molecules involved in innate immunity. 6,7 The TRIM family is characterized by a combination of RING, B-Box, and coiled-coil domains, followed by one of several C-terminal domains. 13 To date, nearly 70 TRIM family members have been identified, yet the most intensively studied TRIM protein may be

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supporting

confidence: 53%

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

et al. 2009

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“…30 A number of the genes that are upregulated in the 'inheritance' signature have previously been implicated in AA pathogenesis (TNF, TRAF1, CTLA4, IL1RN, ICAM1) 9,10 or other autoimmune diseases (NKTR, IL-6 signal transducer). 31,32 These findings reflect an activated immune system in AA-prone individuals with enhanced inflammatory cytokine expression and the enhanced expression of genes promoting trans-endothelial cell migration.…”

Section: Resultsmentioning

confidence: 91%

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

Coda¹,

Hysa²,

Seiffert-Sinha³

et al. 2010

Genes Immun

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Alopecia areata (AA) is an autoimmune hair loss disorder in which systemic disturbances have been described, but are poorly understood. To evaluate disease mechanisms, we examined gene expression in the blood of defined clinical subgroups (patchy AA persistent type, AAP, n ¼ 5; alopecia universalis, AU, n ¼ 4) and healthy controls (unaffected relatives, UaR, n ¼ 5; unaffected non-relatives, UaNR, n ¼ 4) using microarrays. Unsupervised hierarchical clustering separates all four patient and control groups, producing three distinct expression patterns reflective of 'inheritance', 'disease' and 'severity' signatures. Functional classification of differentially expressed genes (DEGs) comparing disease (AAP, AU) vs normal (UaR) groups reveals upregulation in immune response, cytokine signaling, signal transduction, cell cycle, proteolysis and cell adhesionrelated genes. Pathway analysis further reveals the activation of several genes related to natural killer-cell cytotoxicity, apoptosis, mitogen activated protein kinase, Wnt signaling and B-and T-cell receptor signaling in AA patients. Finally, 35 genes differentially expressed in AA blood overlap with DEGs previously identified in AA skin lesions. Our results implicate innate and adaptive immune processes while also revealing novel pathways, such as Wnt signaling and apoptosis, relevant to AA pathogenesis. Our data suggest that peripheral blood expression profiles of AA patients likely carry new biomarkers associated with disease susceptibility and expression.

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“…Recently, microarray analyses has been used by other investigators to study differential gene expression patterns in SLE patients as compared with healthy controls. [32][33][34][35][36][37] In this study, we investigated differential gene expression in the splenic cells of pConstolerized BWF1 mice to cells from unmanipulated BWF1 mice to better understand the molecular mechanisms of suppression/tolerance. We investigated genes that are differentially expressed after pCons treatment in BWF1 mice in splenic white blood cells (WBC), CD4 þ T cells and CD8 þ T cells.…”

Section: Introductionmentioning

confidence: 99%

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

et al. 2010

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Tolerizing mice polygenically predisposed to lupus-like disease (NZB/NZW F1 females) with a peptide mimicking anti-DNA IgG sequences containing MHC class I and class II T cell determinants (pConsensus, pCons) results in protection from full-blown disease attributable in part to the induction of CD4 þ CD25 þ Foxp3 þ and CD8 þ Foxp3 þ regulatory T cells. We compared 45 000 murine genes in total white blood cells (WBC), CD4 þ T cells, and CD8 þ T cells from splenocytes of (NZBxNZW) F1 lupus-prone mice tolerized with pCons vs untreated naïve mice and found two-fold or greater differential expression for 448 WBC, 174 CD4, and 60 CD8 genes. We identified differentially expressed genes that played roles in the immune response and apoptosis. Using real-time PCR, we validated differential expression of selected genes (IFI202B, Bcl2, Foxp3, Trp-53, CCR7 and IFNar1) in the CD8 þ T cell microarray and determined expression of selected highly upregulated genes in different immune cell subsets. We also determined Smads expression in different immune cell subsets, including CD4 þ T cells and CD8 þ T cells, to detect the effects of TGF-b, known to be the major cytokine that accounts for the suppressive capacity of CD8 þ Treg in this system. Silencing of anti-apoptotic gene Bcl2 or interferon genes (IFI202b and IFNar1 in combination) in CD8 þ T cells from tolerized mice did not affect the expression of the other selected genes. However, silencing of Foxp3 reduced expression of Foxp3, Ifi202b and PD1-all of which are involved in the suppressive capacity of CD8 þ Treg in this model.

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Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus

Cited by 41 publications

References 56 publications

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

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