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Osteoporosis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Mazen Nasrallah, Marcy B. Bolster
Sema4D inhibition. Sema4D is expressed by osteoclasts and inhibits osteoblast differentiation / bone formation through interaction with PlexinB1 on the surface of osteoblasts. Sema4D inhibition may be a promising novel anabolic therapy.47
Osteoimmunology in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Lia Ginaldi, Daniela Di Silvestre, Maria Maddalena Sirufo, Massimo De Martinis
Many other receptor pathways, most of which are shared by immune cells, interact with RANK, some co-stimulators and others inhibitors. The inhibitor receptor system ephrin (Eph) B2/B4 allows the passage of signals bidirectionally between osteoclasts and osteoblasts [54]. It inhibits osteoclast differentiation by blocking c-fos and the NFATc1 transcriptional cascade in osteoclast cell lineage and contemporaneously favors the coupling of bone formation and resorption through the induction of osteogenetic regulatory genes in osteoblasts [55]. The ephrinB2/ephrinB4 binding therefore functions as a coupling factor in bone remodeling process [56]. Other coupling factors are semaphorins, glycoproteins involved in several biological processes such as immune response, tumor progression, and bone remodeling, among others [57–59]. Semaphorin4D (Sema4D) expressed in osteoclasts binds to its osteoblast receptor (Plexin-B1) inhibiting IGF-1 pathway, essential for osteoblast differentiation [60], whereas Sema3A in osteoblasts is an inhibitor of osteoclastogenesis [61]. During bone remodeling osteoclasts inhibit bone formation by expressing Sema4D, in order to initiate bone resorption, whereas osteoblasts express Sema3A that suppresses bone resorption, prior to bone formation.
Semaphorin 4D as a guidance molecule in the immune system
Published in International Reviews of Immunology, 2021
Semaphorin 4D (Sema4D) is a multifunctional molecule that is widely represented in various tissues and involved in different physiological processes. Being a typical member of the semaphorin family, it plays a key role in axon guidance, serving primarily as a repulsive factor – similar to a semaphore, hence the name of the family [1–3]. Along with the control of neurogenesis, Sema4D is involved in angiogenesis, osteogenesis, as well as in the development and function of the immune system [4–7]. Structurally, Sema4D is a transmembrane glycoprotein weighing 150 kDa, which is expressed as a disulfide-linked homodimer and can be cleaved from the membrane by proteolysis upon cell activation to form a soluble homodimer (sSema4D), which retains the function of its membrane analog [4, 8, 9].
Components of specific immunity in host defense
Published in International Reviews of Immunology, 2021
The dynamicity of immune cells and soluble mediatiors are key for host defense and immune homeostasis. It is mediated through Immune cell trafficking via complex signaling pathways. The movement of immune cells are primarily supported by cell surface molecule like leukocyte adhesion molecules, integrins, lectins, tetraspanines, and/or induction of chemokines and chemokine receptors and so on. A member of the semaphorin family protein known as semaphorin 4 D (Sema4D) is reported to play an important role in axon guidance and an important role in immunity, particularly, cell migration. The second review in this issue by Kuklin et al. discusses the role of Sema4D in immune regulation in cell migration. The article also discusses the underline molecular mechanism of Sema4D-mediated cell migration [2]. This article will be interesting to immunologists, neurologists, and scientists working in neuroimmunology (Figure 1).
Sema4D correlates with tumour immune infiltration and is a prognostic biomarker in bladder cancer, renal clear cell carcinoma, melanoma and thymoma
Published in Autoimmunity, 2021
Qiongyu Lu, Ping Cai, Yan Yu, Ziting Liu, Guona Chen, Zhao Zeng
The role of Sema4D in the immune system including autoimmune disease has been well studied [30,31]. Sema4D commonly interacts with its low affinity receptor CD72 in the immune system [9]. Sema4D is highly expressed in resting T cells, and activated B cells and APCs [1,32]. Sema4D was reported to promote the aggregation and survival of B cells, and enhance the antibody production, and the activation and maturation of APCs via interacting with CD72 [1,32,33]. Sometimes, Sema4D might act as a receptor to regulate T cell activation and B cell terminal differentiation [34–36]. In addition, lack of Sema4D resulted in a reduction of tumour-macrophages in tumour microenvironment, although the mechanism is still unclear [24]. High expression of Sema4D influences the infiltration and distribution of leukocytes in tumour microenvironment [37]. Blockade of Sema4D promoted immune cell infiltration and enhanced response to immunotherapies [37]. All these studies suggested that engagement of Sema4D and its receptors play an important role in tumour progression. In this study, we comprehensively analysed the correlation of Sema4D expression with tumour immune infiltration and prognosis of pan-cancer in TCGA.