Increased Production of Macrophage Migration Inhibitory Factor by T Cells in Patients with IgA Nephropathy

2001 ◽  
Vol 21 (6) ◽  
pp. 455-464 ◽  
Author(s):  
Koichi Matsumoto ◽  
Katsuo Kanmatsuse
Keyword(s):  
T Cells ◽  
Iga Nephropathy ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration

scholarly journals Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma

2019 ◽  
Vol 9 (10) ◽  
pp. 284 ◽  
Author(s):  
Eugenio Cavalli ◽  
Emanuela Mazzon ◽  
Santa Mammana ◽  
Maria Basile ◽  
Salvo Lombardo ◽  
...  
Keyword(s):  
T Cells ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Cytotoxic T Cells ◽  
Hdac Inhibitors ◽  
Inhibitory Factor ◽  
Mycn Amplification ◽  
Macrophage Migration ◽  
Dopachrome Tautomerase

Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts several overlapping functions with MIF. Growing evidence suggests a key role for MIF and DDT in the development of cancer. The aim of this study is to characterize the prognostic value of MIF and DDT in NB. We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification. Moreover, higher levels of MIF are mostly enriched by Th1 cells, while lower levels of MIF are associated with an increased proportion of B cells, Cytotoxic T cells, Dendritic cells and Natural Killer T cells. We also show that treatment with the histone deacetylase (HDAC) inhibitor, vorinostat, of the NB cell line, SH-SY5Y, determines a significant reduction in the expression of both MIF and DDT. Finally, MIF and DDT inhibition by short interfering RNA is able to revert vincristine sensitivity in vitro. Overall, our data suggest that MIF exert pro-tumorigenic properties in NB, likely by dampening antigen presentation and cytotoxic immune responses, and we propose the HDAC inhibitors as a potential therapeutic strategy for NB patients.

scholarly journals Macrophage Migration Inhibitory Factor Promotes the Interaction between the Tumor, Macrophages, and T Cells to Regulate the Progression of Chemically Induced Colitis-Associated Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Thalia Pacheco-Fernández ◽  
Imelda Juárez-Avelar ◽  
Oscar Illescas ◽  
Luis I. Terrazas ◽  
Rogelio Hernández-Pando ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Intestinal Epithelium ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Chemical Carcinogenesis ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Initial Development ◽  
The Impact

Colitis-associated colorectal cancer (CRC) development has been shown to be related to chronically enhanced inflammation. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator that favors inflammatory cytokine production and has chemotactic properties for the recruitment of macrophages (Møs) and T cells. Here, we investigated the role of MIF in the inflammatory response and recruitment of immune cells in a murine model of chemical carcinogenesis to establish the impact of MIF on CRC genesis and malignancy. We used BALB/c MIF-knockout (MIF-/-) and wild-type (WT) mice to develop CRC by administering intraperitoneal (i.p.) azoxymethane and dextran sodium sulfate in drinking water. Greater tumor burdens were observed in MIF-/- mice than in WT mice. Tumors from MIF-/- mice were histologically identified to be more aggressive than tumors from WT mice. The localization of MIF suggests that it is also involved in cell differentiation. The relative gene expression of il-17, measured by real-time PCR, was higher in MIF-/- CRC mice, compared to the WT CRC and healthy MIF-/- mice. Importantly, compared to the WT intestinal epithelium, lower percentages of tumor-associated Møs were found in the MIF-/- intestinal epithelium. These results suggest that MIF plays a role in controlling the initial development of CRC by attracting Møs to the tumor, which is a condition that favors the initial antitumor responses.

scholarly journals Upregulated Expression of Macrophage Migration Inhibitory Factor, Its Analogue D-Dopachrome Tautomerase, and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 667 ◽  
Author(s):  
Cavalli ◽  
Mazzon ◽  
Basile ◽  
Mangano ◽  
Di Marco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Migration Inhibitory Factor ◽  
Cd4 T Cells ◽  
Macrophage Migration Inhibitory Factor ◽  
Clinically Isolated Syndrome ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Healthy Controls ◽  
Dopachrome Tautomerase

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.

Donor -173 G/C Polymorphism of Macrophage Migration Inhibitory Factor Gene Is Associated with the Development of Chronic Graft Versus Host Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2873-2873
Author(s):  
Yayi Chang ◽  
Ernst Holler ◽  
Heike Bremm ◽  
Hildegard T. Greinix ◽  
Reinhard Andreesen ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Graft Versus Host Disease ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

Abstract Chronic graft versus host disease (cGVHD) severely impairs the clinical outcome and quality of life after allogeneic stem cell transplantation (allo-SCT). cGVHD pathophysiology is not fully understood, and treatment often fails. The cytokine macrophage migration inhibitory factor (MIF) is produced by various cell types including T cells, macrophages, epithelial cells and the pituitary gland. It shows a broad range of immunostimulatory and proinflammatory properties. In addition, MIF overrides the inhibitory immunological effects of glucocorticoids, which are an important therapeutic tool both in acute GVHD (aGVHD) and cGVHD. As MIF has been associated with various inflammatory diseases, which pathophysiologically share similarities to cGVHD, we assessed the possible contribution of the −173 G/C polymorphism of the MIF gene in cGVHD development. The presence of the C allele is known to be associated with increased cellular MIF production and elevated serum MIF levels in the context of inflammation, but not in healthy individuals. We genotyped 332 donor-recipient pairs of patients receiving allo-SCT from related (n=115) or unrelated (n=217) donors at two independent SCT centers. Stem cells were derived from bone marrow (n=120) or from peripheral blood stem cells (n=222) and T cell depletion (TCD) was performed in 106 cases. Mean follow up was 654±687 days. The C allele (GC or CC genotype) was present in 27.2% of recipients and 25.7% of donors. Overall, 41.8% of transplanted patients developed cGVHD. The incidence of cGVHD development rose from 39.5% in donor/recipient pairs both carrying the GG genotype to 52.2% in those pairs, in which donors carried the GC or CC genotype (p=0.046). Presence of the C allele in the recipient did not significantly contribute to cGVHD development (p=0.26). As T cells are a major source of MIF and have been associated with cGVHD, we next tested the impact of donor T cells carrying the C allele in the context of TCD. As expected, cGVHD incidence was significantly increased in patients receiving non-TCD allo-SCT from GC or CC donors compared to recipients of GG genotype cells (55.1% versus 38.2%; p=0.045). In contrast, when TCD was performed, transplantation of either cells with the C allele or with GG donor cells did not result in differences in cGVHD (44.4% versus 38.0%; p=0.78). Finally we analyzed, whether this polymorphism has any effects on the development of aGVHD. In total, 52.6% of patients developed aGVHD >/= 2, and the incidence of aGVHD was directly associated with the development of cGVHD (p<0.001). However no association between the onset of aGVHD and the G/C polymorphism of either the donor or the recipient was seen. Collectively, our data show, that the risk of developing cGVHD is increased after allo-SCT, when the donor but not the recipient has a G to C transition at position −173 of the MIF gene. Most likely, donor T cells are critical, as this observation vanishes when TCD is performed. Interestingly, carrying the C allele is not a risk factor for aGVHD development, therefore demonstrating a heretofore unknown distinct and independent property of donor T cells in the pathophysiology of cGVHD. Animal studies targeting MIF signaling are ongoing, and in future this may prove as a beneficial and promising approach to decrease the incidence and severity of this serious complication after allo-SCT.

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