CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells

Solstad, Therese; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd; Taskén, Kjetil; Torgersen, Knut Martin

doi:10.1182/blood-2011-02-339242

Cited by 72 publications

(62 citation statements)

References 51 publications

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“…The proteomics data set with its 5225 identified proteins by itself is a valuable repository for further Treg research. Although proteomics has been used to study Tregs, previous studies focused either on proteins identified by gel blotting (44) or selective differences in the expression of specific surface molecules (45) or protein kinases (46). One recent report used proteomics to study the FOXP3 complex with all of its interaction partners (47).…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

Barra

Richards

Hansson

et al. 2015

The Journal of Immunology

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Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus. Reduced levels of TCF7, found in the heterozygote, resulted in a greater potential for Treg precursors to differentiate into the Treg lineage. In contrast, activation of TCF7 through β-catenin had the opposite effect. TCF7 levels influenced the required TCR signaling strength of Treg precursors, and TCF7 deficiency broadened the repertoire and allowed lower TCR affinities to be recruited into the Treg lineage. FOXP3 was able to repress TCF7 protein expression. In summary, we propose a regulatory role for TCF7 in limiting access to the Treg lineage.

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Section: Discussionmentioning

confidence: 99%

Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

Barra

Richards

Hansson

et al. 2015

The Journal of Immunology

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“…Protein identifications were performed as described previously (Solstad et al, 2011;Solstad et al, 2010).…”

Section: Protein Identification By Lc-ms/msmentioning

confidence: 99%

A PKA-ezrin-connexin 43 signaling complex controls gap junction communication and thereby trophoblast cell fusion

Pidoux

Gerbaud

Dompierre

et al. 2014

Journal of Cell Science

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Cell fusion occurs as part of the differentiation of some cell types, including myotubes in muscle and osteoclasts in remodeling bone. In the human placenta, mononuclear cytotrophoblasts in a human chorionic gonadotropin (hCG)-driven process fuse to form multinucleated syncytia that allow the exchange of nutrients and gases between the maternal and fetal circulation. Experiments in which protein kinase A (PKA) is displaced from A-kinase anchoring proteins (AKAPs), or in which specific AKAPs are depleted by siRNA-mediated knockdown, point to ezrin as a scaffold required for hCG-, cAMP-and PKA-mediated regulation of the fusion process. By a variety of immunoprecipitation and immunolocalization experiments, we show that ezrin directs PKA to a molecular complex of connexin 43 (Cx43, also known as GJA1) and zona occludens-1 (ZO-1, also known as TJP1). A combination of knockdown experiments and reconstitution with ezrin or Cx43 with or without the ability to bind to its interaction partner or to PKA demonstrate that ezrin-mediated coordination of the localization of PKA and Cx43 is necessary for discrete control of Cx43 phosphorylation and hCG-stimulated gap junction communication that triggers cell fusion in cytotrophoblasts.

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“…Among the immune-response genes, TNFRSF8 and BSG attracted our interest because these genes were upregulated in the PP samples (Fig. 3A) and encode the activation markers CD30 and CD147, which have been associated with regulatory T cells (14,15), Th2-like response, and chronic T-cell stimulation (16,17), although these genes are also detected in other immune cell subsets (18). In addition, TNFRSF8 upregulation was associated with several downregulated genes in the "inflammatory response, cell death and cell-mediated immune response" IPA pathway network shown in Fig.…”

Section: Validation Studies Confirm Differential Gene Expression Pattmentioning

confidence: 99%

Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

et al. 2014

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Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients. Biopsies from positive nodes were selected for comparable tumor infiltration, presence or absence of further regional node metastases, and relapse at 5-year follow-up. Unsupervised analysis of gene expression profiles revealed immune response to be a major gene ontogeny represented. Among genes upregulated in patients with progressing disease, the TNF receptor family member CD30/TNFRSF8 was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30 þ lymphocytes in nodes from progressing patients compared with nonprogressing patients. Phenotypic profiling demonstrated that CD30 þ lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4 þ Foxp3 þ or PD1 þ subpopulations and CD4 À CD8 À T cells. CD30 þ T lymphocytes were increased in peripheral blood lymphocytes of melanoma patients at advanced disease stages. Our findings reinforce the concept that sentinel nodes act as pivotal sites for determining progression patterns, revealing that the presence of CD30 þ lymphocytes at those sites associate positively with melanoma progression. Cancer Res; 74(1); 130-40. Ó2014 AACR.

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CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+CTLA4+-activated human regulatory T cells

Cited by 72 publications

References 51 publications

Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus

A PKA-ezrin-connexin 43 signaling complex controls gap junction communication and thereby trophoblast cell fusion

Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression

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