Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

Naka, Erika Lamkowski; Ponciano, Viviane Campos; Cenedeze, Marcos Antônio; Pacheco-Silva, Álvaro; Câmara, Niels Olsen Saraiva

doi:10.1016/j.intimp.2008.11.013

Cited by 24 publications

(16 citation statements)

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“…Gal-9 can influence the immune system in different ways [6], either by exacerbating the inflammatory process [7] or by exhibiting therapeutic effects in autoimmune disease models, such as autoimmune arthritis, experimental allergic encephalomyelitis, and type 1 diabetes mellitus. Notably, it is generally believed that the engagement of Gal-9 by its receptor TIM-3 established the Gal-9/TIM-3 pathway as a novel regulator of Th1 immunity and tolerance induction [8].…”

Section: Introductionmentioning

confidence: 99%

Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

et al. 2015

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a b s t r a c tIntroduction: Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM-3 have been demonstrated to be present on immune cells suggesting general involvement in immunosuppression such as fetomaternal tolerance. The aim of our study was to investigate the expression pattern of PD-1, TIM-3, and its ligand Gal-9 on different immune cell subsets in the peripheral blood and at the fetomaternal interface in pregnant mice. Methods: TIM-3 and PD-1 expression by peripheral and decidual immune cells from pregnant BALB-c mice in 2 weeks of gestational age were measures by flow cytometry. Placental galectin-9 expression was determined by immunohistochemically and RT-PCR. Results: Gal-9 was found to be present in the spongiotrophoblast layer of the haemochorial placenta.Decidual NK, NKT and g/d T cells showed increased PD-1 expression and reduced cytotoxic potential when compared to the periphery. TIM-3 expression by NK cells and g/d T cells is similar both in the periphery and in the decidua, notably, their relative TIM-3 expression is increased locally which is associated with reduced lytic activity. Decidual NKT cells exhibit a reduced TIM-3 expression with increased relative receptor expression and a slightly increased cytotoxicity when compared to the periphery. Discussion: Our data reveals a particularly complex, tissue and cell type specific immunoregulatory mechanism by the investigated co-inhibitory receptors at the fetomaternal interface.

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Section: Introductionmentioning

confidence: 99%

Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

et al. 2015

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“…Identification of Galectin-9 (Gal-9) as a ligand for TIM-3 has established the Gal-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction [27,32,33]. Engagement of TIM-3 by its ligand Gal-9 negatively regulates IFN-γ secretion, influences the ability to induce T cell tolerance and triggers a significant signal cascade to induce apoptosis of Th1 type immune cells.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia

et al. 2013

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BackgroundPreeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction.MethodsThe aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry.ResultsInvestigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56dim NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56dim NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia.ConclusionThese data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered Galectin-9 and TIM-3 expression could result an enhanced systemic inflammatory response including the activation of Th1 lymphocytes in preeclampsia.

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“…64 In allograft nephrectomy samples from patients suffering acute rejection, TIM-3 and galectin-9 mRNA expression patterns correlated with severity of rejection. 65 A number of animal allograft rejection models have demonstrated potential benefits for anti-CTLA-4Ab, paving the way for clinical trials. 66–68 Belatacept (Nulojix) is a CTLA-4fusion protein that differs from Abatacept by two amino acids; it is equivalent in immunosuppressive efficacy to cyclosporine 6 months after renal transplantation from living donors.…”

Section: Deficient T-cell Inhibitionresulting In T-cell Overactivitymentioning

confidence: 99%

T-cell Inhibitors

Das¹,

Ariizumi²,

Cruz³

2012

Dermatitis

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Allergic contact dermatitis is the quintessential example of a delayed-in-time and T cell-mediated immune response. In the last decade, many of the molecular events required to initiate (or block) such a response have been uncovered. Textbook and journal reviews have emphasized the co-stimulatory requirements, with less focus on the co-inhibitory signals that are of equal importance in understanding this central event of adaptive immunity. To fill this gap, we offer a compendium of discoveries characterizing the ligand/receptor pairs inhibiting T-cell activation and of selected illnesses and therapeutic applications that illuminate their role in health and disease.

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Detection of the Tim-3 ligand, galectin-9, inside the allograft during a rejection episode

Cited by 24 publications

References 24 publications

Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia

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