Signaling from membrane semaphorin 4D in T lymphocytes

Куклина, Е. М.; Nekrasova, I. V.; Glebezdina, N. S.

doi:10.1016/j.molimm.2020.08.009

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…This AHNAK-dependent calcium signaling is also upregulated during CD4+ T cell activation [ 40 , 41 ] and a knockout of AHNAK inhibits T cell responses and the secretion of IFN-γ and IL-4 cytokines [ 42 ]. SEMA4D regulates cell proliferation by interacting with CD72 [ 43 , 44 ]. It downregulates the differentiation of regulatory T (Treg) cells by inhibiting Foxp3 expression [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Effects on the Translation of Immune-Related Alternatively Polyadenylated mRNAs in Melanoma and T Cells by eIF4A Inhibition

Biswas

Guemiri

Cadix

et al. 2022

Cancers

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Targeting the translation initiation complex eIF4F, which binds the 5′ cap of mRNAs, is a promising anti-cancer approach. Silvestrol, a small molecule inhibitor of eIF4A, the RNA helicase component of eIF4F, inhibits the translation of the mRNA encoding the signal transducer and activator of transcription 1 (STAT1) transcription factor, which, in turn, reduces the transcription of the gene encoding one of the major immune checkpoint proteins, i.e., programmed death ligand-1 (PD-L1) in melanoma cells. A large proportion of human genes produce multiple mRNAs differing in their 3′-ends through the use of alternative polyadenylation (APA) sites, which, when located in alternative last exons, can generate protein isoforms, as in the STAT1 gene. Here, we provide evidence that the STAT1α, but not STAT1β protein isoform generated by APA, is required for silvestrol-dependent inhibition of PD-L1 expression in interferon-γ-treated melanoma cells. Using polysome profiling in activated T cells we find that, beyond STAT1, eIF4A inhibition downregulates the translation of some important immune-related mRNAs, such as the ones encoding TIM-3, LAG-3, IDO1, CD27 or CD137, but with little effect on the ones for BTLA and ADAR-1 and no effect on the ones encoding CTLA-4, PD-1 and CD40-L. We next apply RT-qPCR and 3′-seq (RNA-seq focused on mRNA 3′ ends) on polysomal RNAs to analyze in a high throughput manner the effect of eIF4A inhibition on the translation of APA isoforms. We identify about 150 genes, including TIM-3, LAG-3, AHNAK and SEMA4D, for which silvestrol differentially inhibits the translation of APA isoforms in T cells. It is therefore crucial to consider 3′-end mRNA heterogeneity in the understanding of the anti-tumor activities of eIF4A inhibitors.

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Section: Resultsmentioning

confidence: 99%

Differential Effects on the Translation of Immune-Related Alternatively Polyadenylated mRNAs in Melanoma and T Cells by eIF4A Inhibition

Biswas

Guemiri

Cadix

et al. 2022

Cancers

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“…Adiponectin binds directly to CD100 and inhibits the cleavage of the 150-kDa full-length molecule to form the 120-kDa species that interacts with plexin B1, a high-affinity receptor on epithelial cells 46 , or other surface glycoproteins, such as galectin-3. In WT TNC complexes, CD100 presents mainly as the 150-kDa species to form the membrane tethering structures containing adiponectin, Nrp1 and/or CD72, a low-affinity receptor expressed on B-cells 47 . When binding to CD72, CD100 suppresses the negative signals to enhance the response of B-cell antigen receptor 48 .…”

Section: Discussionmentioning

confidence: 99%

Adiponectin-expressing Treg facilitate T lymphocyte development in thymic nurse cell complexes

et al. 2021

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Adiponectin is a well-known insulin sensitizer and anti-inflammatory molecule, possessing therapeutic potentials in cardiovascular, metabolic and cancer diseases. Results of the present study demonstrate that adiponectin is expressed in a population of regulatory T-cells (Treg) resided within the thymic nurse cell (TNC) complexes. Adoptive transfer of adiponectin-expressing Treg precursors effectively attenuated obesity, improved glucose and insulin tolerance, prevented fatty liver injuries in wild-type mice fed a high-fat diet, and significantly inhibited breast cancer development in MMTV-PyVT transgenic mice. Within the TNC complexes, locally produced adiponectin bound to and regulated the expression as well as the distribution of CD100, a transmembrane lymphocyte semaphorin, in turn modulating the lymphoepithelial interactions to facilitate T-cell development and maturation. In summary, adiponectin plays an important role in the selection and development of T lymphocytes within the TNC complexes. Adiponectin-expressing Treg represent a promising candidate for adoptive cell immunotherapy against obesity-related metabolic and cancer diseases.

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“…Furthermore, Sema4A receptors are highly expressed in various immune cells, including macrophages and lymphocytes during lung inflammation (15). Semaphorin 4D (Sema4D), mainly expressed in T and B immune cells, is another transmembrane protein that regulates macrophage activity by stimulating cytokine synthesis (12,(16)(17)(18). In addition, Sema4D induces inflammation by enhancing B cell activation (19).…”

Section: Introductionmentioning

confidence: 99%

Relationship of Semaphorin Proteins with Blood Markers in Patients with COVID-19

Okuyan,

Doğan,

Bal

et al. 2023

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Amaç: COVID salgını dünya çapında sosyo-ekonomik yaşamı ve sağlık sistemlerini etkileyen ciddi bir sağlık sorunudur. Semaforinlerin bazı hastalıklardaki rolü nispeten bilinmesine rağmen, bu moleküllerin COVID-19'un patogenezi ile ilişkisi belirsizliğini koruyor. Bu nedenle, Semaforinlerin (Sema3A, Sema4A, Sema4D ve Sema7A) biyokimyasal ve inflamatuar değişikliklerle ilişkisini ve COVID-19 hastalarında hastalık varlığını ve hastalık şiddetini öngörmedeki rollerini araştırmayı amaçladık. Gereç ve Yöntem: Bu çalışmaya toplam 144 COVID-19 hastası ve 20 sağlıklı birey dahil edildi. Serum Semaforinleri, Enzime bağlı İmmünosorbent Tahlili kullanılarak analiz edildi. Diğer laboratuvar parametreleri, rutin laboratuvar teknikleri kullanılarak ölçüldü. Bulgular: Sema3A konsantrasyonları, sağlıklı kontrollerle karşılaştırıldığında hem şiddetli hem de şiddetli olmayan COVID-19 grubundaki hastalarda yüksekti (p<0.0001). Şiddetli COVID-19 grubundaki hastalarda Sema4A seviyeleri anlamlı olarak azaldı (p=0.002). Sema3A, EOS, RBC, HGB, HCT ve MCV gibi rutin hematolojik belirteçlerle negatif korelasyon gösterdi. Ayrıca Sema3A, D-dimer ve fibrinojen gibi pıhtılaşma belirteçleri ve ESR, CRP, PCT ve ferritin gibi inflamatuar belirteçler ve ALT, AST, BUN, CK ve LDH gibi biyokimyasal belirteçler ile pozitif korelasyon göstermiştir. Sema4A, WBC ile negatif korelasyon gösterirken, LYM ve HCT ile pozitif korelasyon gösterdi. 3,03 ng/mL'nin üzerindeki Sema3A seviyeleri ve 11,8ng/mL'nin altındaki Sema4A konsantrasyonları COVID-19'un varlığını öngörebilir (sırasıyla p<0,0001, p=0,02). Sonuç: Burada sunulan verilerimiz, Sema3A ve Sema4A'nın COVID-19 için tanısal belirteçler olabileceğini ve hastalığın klinik yönetiminde önemi olabileceğini düşündürmektedir.

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Signaling from membrane semaphorin 4D in T lymphocytes

Cited by 7 publications

References 23 publications

Differential Effects on the Translation of Immune-Related Alternatively Polyadenylated mRNAs in Melanoma and T Cells by eIF4A Inhibition

Differential Effects on the Translation of Immune-Related Alternatively Polyadenylated mRNAs in Melanoma and T Cells by eIF4A Inhibition

Adiponectin-expressing Treg facilitate T lymphocyte development in thymic nurse cell complexes

Relationship of Semaphorin Proteins with Blood Markers in Patients with COVID-19

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