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  1. Book ; Online: Dendritic Cells

    Svetlana P. Chapoval

    2018  

    Abstract: Since their discovery in 1973 by Zanvil Cohn and Ralph Steinman (Nobel Prize in Physiology and Medicine, 2011), dendritic cells (DCs) continue to intrigue research scientists as their new markers, subpopulations and properties are being detected and the ... ...

    Abstract Since their discovery in 1973 by Zanvil Cohn and Ralph Steinman (Nobel Prize in Physiology and Medicine, 2011), dendritic cells (DCs) continue to intrigue research scientists as their new markers, subpopulations and properties are being detected and the relevant literature is being doubled each year. This book combines the most comprehensive reviews of several critical aspects of DC biology and function written by a group of international experts in the field. The first section briefly discusses recent advances in DC subtypes, phenotypes, and functions in different diseases. The following sections look closely at DC phenotyping, DC-NK cell interplay, and roles of DC in bone loss and repair and parasitic infections. The final section on DC and cancer includes perspectives on DC vaccination based on modifications and therapeutic applications.
    Keywords Life Sciences ; Biochemistry ; Genetics and Molecular Biology ; Immunology
    Language English
    Publisher IntechOpen
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation

    Apoorva S. Iyer / Svetlana P. Chapoval

    International Journal of Molecular Sciences, Vol 20, Iss 1, p

    A Promoter or a Suppressor?

    2018  Volume 124

    Abstract: Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons ... ...

    Abstract Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function, instructing a fine tuning of the immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro- or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.
    Keywords neuroimmune semaphorins ; plexins ; cancer ; angiogenesis ; inflammation ; VEGF ; Sema4A ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Identifying Function Determining Residues in Neuroimmune Semaphorin 4A

    Svetlana P. Chapoval / Mariah Lee / Aaron Lemmer / Oluwaseyi Ajayi / Xiulan Qi / Andrew F. Neuwald / Achsah D. Keegan

    International Journal of Molecular Sciences, Vol 23, Iss 3024, p

    2022  Volume 3024

    Abstract: Semaphorin 4A (Sema4A) exerts a stabilizing effect on human Treg cells in PBMC and CD4+ T cell cultures by engaging Plexin B1. Sema4A deficient mice display enhanced allergic airway inflammation accompanied by fewer Treg cells, while Sema4D deficient ... ...

    Abstract Semaphorin 4A (Sema4A) exerts a stabilizing effect on human Treg cells in PBMC and CD4+ T cell cultures by engaging Plexin B1. Sema4A deficient mice display enhanced allergic airway inflammation accompanied by fewer Treg cells, while Sema4D deficient mice displayed reduced inflammation and increased Treg cell numbers even though both Sema4 subfamily members engage Plexin B1. The main objectives of this study were: 1. To compare the in vitro effects of Sema4A and Sema4D proteins on human Treg cells; and 2. To identify function-determining residues in Sema4A critical for binding to Plexin B1 based on Sema4D homology modeling. We report here that Sema4A and Sema4D display opposite effects on human Treg cells in in vitro PBMC cultures; Sema4D inhibited the CD4+CD25+Foxp3+ cell numbers and CD25/Foxp3 expression. Sema4A and Sema4D competitively bind to Plexin B1 in vitro and hence may be doing so in vivo as well. Bayesian Partitioning with Pattern Selection (BPPS) partitioned 4505 Sema domains from diverse organisms into subgroups based on distinguishing sequence patterns that are likely responsible for functional differences. BPPS groups Sema3 and Sema4 into one family and further separates Sema4A and Sema4D into distinct subfamilies. Residues distinctive of the Sema3,4 family and of Sema4A (and by homology of Sema4D) tend to cluster around the Plexin B1 binding site. This suggests that the residues both common to and distinctive of Sema4A and Sema4D may mediate binding to Plexin B1, with subfamily residues mediating functional specificity. We mutated the Sema4A-specific residues M198 and F223 to alanine; notably, F223 in Sema4A corresponds to alanine in Sema4D. Mutant proteins were assayed for Plexin B1-binding and Treg stimulation activities. The F223A mutant was unable to stimulate Treg stability in in vitro PBMC cultures despite binding Plexin B1 with an affinity similar to the WT protein. This research is a first step in generating potent mutant Sema4A molecules with stimulatory function for Treg cells with a ...
    Keywords Semaphorin 4A ; Plexin B1 ; human Treg cells ; mutated proteins ; immunotherapeutics for asthma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570 ; 572
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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