Frequency of dendritic cell subsets and ILT3, ILT4 gene expression in two different immunosuppressive protocols in kidney transplant recipients. A cohort report

Karimi, Mozhdeh; Ahmadpoor, Pedram; Nafar, Mohsen; Pour-Reza-Gholi, Fatemeh; Jamali, Saeideh; Eteghadi, Atefeh; Yekaninejad, Mir Saeed; Amirzargar, Ali Akbar

doi:10.1007/s11033-019-05113-x

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…Unexpectedly, ILT-4 did not present a difference when comparing stable cases with acute rejection but of interest, we did observe a close to significant down-regulation of ILT-4 within stable cases either when anti-IL2αR antibody was used (P = 0.08) or when RAPA substituted for MMF (P = 0.1). We speculate that if we had the opportunity to include a larger number of cases, these differences could reach a significance level, in line with those observed for ILT-4 by others [14] [51]. Said that, because it is important to acknowledge that still other authors observed in human renal transplants an induction of ILT-3 high and ILT-4 high dendritic cells by RAPA [52].…”

Section: Discussionsupporting

confidence: 79%

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

Xavier¹,

Oliveira²

2021

OJNeph

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Following organ transplantation, the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14-30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2αR and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significantly positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR was clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.

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Section: Discussionsupporting

confidence: 79%

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

Xavier¹,

Oliveira²

2021

OJNeph

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“…Kidney transplantation is the first and most numerous and technically mature of the types of large organ transplantation in China. Immunosuppressive regimens initiated for renal transplant recipients, such as the administration of immunosuppressive drugs such as tacrolimus, mycophenolate mofetil and sirolimus, have been found to induce a rise in the expression of LILRB4 on antigen-presenting cells, thereby inducing cellular tolerance, which facilitates better allograft survival [91]. Meanwhile, the mTOR inhibitor rapamycin is the most commonly used immunosuppressive therapy after renal transplantation [92], and it has been shown that renal transplant recipients suffering from chronic graft nephropathy experience a significant increase in LILRB4 expression in renal biopsy tissues after prolonged rapamycin treatment.…”

Section: Lilrb4 and Transplantation Immune Tolerancementioning

confidence: 99%

LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets

Xiang,

Yin,

Wei

et al. 2024

Biomolecules

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LILRB4, a myeloid inhibitory receptor belonging to the family of leukocyte immunoglobulin-like receptors (LILRs/LIRs), plays a pivotal role in the regulation of immune tolerance. LILRB4 primarily mediates suppressive immune responses by transmitting inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs (ITIMs). This immune checkpoint molecule has gained considerable attention due to its potent regulatory functions. Its ability to induce effector T cell dysfunction and promote T suppressor cell differentiation has been demonstrated, indicating the therapeutic potential of LILRB4 for modulating excessive immune responses, particularly in autoimmune diseases or the induction of transplant tolerance. Additionally, through intervening with LILRB4 molecules, immune system responsiveness can be adjusted, representing significant value in areas such as cancer treatment. Thus, LILRB4 has emerged as a key player in addressing autoimmune diseases, transplant tolerance induction, and other medical issues. In this review, we provide a comprehensive overview of LILRB4, encompassing its structure, expression, and ligand molecules as well as its role as a tolerance receptor. By exploring the involvement of LILRB4 in various diseases, its significance in disease progression is emphasized. Furthermore, we propose that the manipulation of LILRB4 represents a promising immunotherapeutic strategy and highlight its potential in disease prevention, treatment and diagnosis.

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Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer

Deng

Chen

Liu

et al. 2021

Antibody Therapeutics

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Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1–5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology—as immune checkpoint molecules and tumor-supporting factors. Here we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.

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Frequency of dendritic cell subsets and ILT3, ILT4 gene expression in two different immunosuppressive protocols in kidney transplant recipients. A cohort report

Cited by 4 publications

References 19 publications

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

LILRB4 Checkpoint for Immunotherapy: Structure, Mechanism and Disease Targets

Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer

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