An update on potentials and promises of T cell co‐signaling molecules in transplantation

Mardomi, Alireza; Mohammadi, Nabiallah; Khosroshahi, Hamid Tayebi; Abediankenari, Saeid

doi:10.1002/jcp.29369

Cited by 23 publications

(17 citation statements)

References 176 publications

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“…CD244 (SLAMF4) is a transmembrane protein present in NK cells, T cells, and other types of immune cells. This protein is a key cell surface receptor, a member of the signaling lymphocytic activating molecule (SLAM) family, and functions as a receptor in immune regulation (1,2). CD244 mainly binds to the CD48 (another member of the SLAM family) on other immune cells, thus regulating the immune response by a trans interaction (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

Sun

Gang

et al. 2021

Front. Immunol.

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Proteins in the signaling lymphocytic activating molecule (SLAM) family play crucial roles in regulating the immune system. CD244 (SLAMF4) is a protein in this family, and is also a member of the CD2 subset of the immunoglobulin (Ig) superfamily. CD244 is a cell surface protein expressed by NK cells, T cells, monocytes, eosinophils, myeloid-derived suppressor cells, and dendritic cells. CD244 binds to the ligand CD48 on adjacent cells and transmits stimulatory or inhibitory signals that regulate immune function. In-depth studies reported that CD244 functions in many immune-related diseases, such as autoimmune diseases, infectious diseases, and cancers, and its action is essential for the onset and progression of these diseases. The discovery of these essential roles of CD244 suggests it has potential as a prognostic indicator or therapeutic target. This review describes the molecular structure and function of CD244 and its roles in various immune cells and immune-related diseases.

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Section: Introductionmentioning

confidence: 99%

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

Sun

Gang

et al. 2021

Front. Immunol.

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“…Blocking of the CD40/CD40L pathways is well established in the study of facilitating allograft transplantation. Both antibodies targeting CD40 and CD40L have been reported for kidney transplantation [114,115]. CD154 antagonist antibody (MR1) has been used to prevent experimental renal ischemia reperfusion injury (IRI) [116].…”

Section: Targeting Cd40 Contributes To Therapeutic Treatments Of Kidnmentioning

confidence: 99%

“…Mice subjected to IRI under the condition of dual treatment of a MyD88 inhibitor and MR1 had completely restored survival rate, decreased serum creatinine (Cr), blood urea nitrogen (BUN), attenuated tubular damage and apoptosis, and reduced inflammatory cytokines in the kidney [116]. However, applications of anti-CD40L antibodies have limitations due to the development of thromboembolism [114,117]. In the setting of kidney disease, novel approaches such as DNA vaccination or siRNA against the CD40 gene may be a more promising approach.…”

Section: Targeting Cd40 Contributes To Therapeutic Treatments Of Kidnmentioning

confidence: 99%

“…The importance of CD40/CD40L signaling to kidney transplantation has been well studied in that CD40 acts as a co-stimulatory molecule associated with adaptive immunity as well as allograft rejection [14]. Usages of CD40 and CD40L blockade antibodies have been well reviewed in other reports [14,114,128,129]. CD40/CD40L contributes to antibody-mediated rejection (AMR) that is caused by donor-specific HLA antibody (DSA), although targeting CD40L alone is not sufficient to inhibit the production of DSA [114].…”

Section: Cd40 and Cd40l Blockade In Kidney Transplantationmentioning

confidence: 99%

“…Usages of CD40 and CD40L blockade antibodies have been well reviewed in other reports [14,114,128,129]. CD40/CD40L contributes to antibody-mediated rejection (AMR) that is caused by donor-specific HLA antibody (DSA), although targeting CD40L alone is not sufficient to inhibit the production of DSA [114]. Usage of anti-CD40 mAb combined with other co-stimulation blockades has been reported as a promising therapy for prolonging graft survival [130].…”

Section: Cd40 and Cd40l Blockade In Kidney Transplantationmentioning

confidence: 99%

See 2 more Smart Citations

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

Zhang

Breidenbach

Russell

et al. 2020

JCM

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The cluster of differentiation 40 (CD40) is activated by the CD40 ligand (CD40L) in a variety of diverse cells types and regulates important processes associated with kidney disease. The CD40/CD40L signaling cascade has been comprehensively studied for its roles in immune functions, whereas the signaling axis involved in local kidney injury has only drawn attention in recent years. Clinical studies have revealed that circulating levels of soluble CD40L (sCD40L) are associated with renal function in the setting of kidney disease. Levels of the circulating CD40 receptor (sCD40), sCD40L, and local CD40 expression are tightly related to renal injury in different types of kidney disease. Additionally, various kidney cell types have been identified as non-professional antigen-presenting cells (APCs) that express CD40 on the cell membrane, which contributes to the interactions between immune cells and local kidney cells during the development of kidney injury. Although the potential for adverse CD40 signaling in kidney cells has been reported in several studies, a summary of those studies focusing on the role of CD40 signaling in the development of kidney disease is lacking. In this review, we describe the outcomes of recent studies and summarize the potential therapeutic methods for kidney disease which target CD40.

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Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection

Luo

Liao

Zhang

et al. 2022

Bioengineering & Transla Med

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Organ transplantation is the optimal treatment for patients with end-stage diseases.T cell activation is a major contributing factor toward the trigger of rejection. Induction therapy with T cell depleting agent is a common option but increases the risk of severe systemic infections. The ideal therapy should precisely target the allograft.Here, we developed a membrane-anchored-protein PD-L1 (map-PD-L1), which effectively anchored onto the surface of rat glomerular endothelial cells (rgEC). The expression of PD-L1 increased directly with map-PD-L1 concentration and incubation time. Moreover, map-PD-L1 was even stably anchored to rgEC at low temperature. Map-PD-L1 could bind to PD-1 and significantly promote T cell apoptosis and inhibited T cell activation. Using kidney transplantation models, we found that ex vivo perfusion of donor kidneys with map-PD-L1 significantly protected grafts against acute injury without using any immunosuppressant. We found map-PD-L1 could reduce T cell graft infiltration and increase intragraft Treg infiltration, suggesting a long-term effect in allograft protection. More importantly, modifying donor organs in vitro was not only safe, but also significantly reduced the side effects of systemic application. Our results suggested that ex vivo perfusion of donor organ with map-PD-L1 might provide a viable clinical option for organ-targeted induction therapy in organ transplantation.

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An update on potentials and promises of T cell co‐signaling molecules in transplantation

Cited by 23 publications

References 176 publications

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

Ex vivo anchored PD‐L1 functionally prevent in vivo renal allograft rejection

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