Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery

Clemente, T.; Vieira, N.J.; Cerliani, Juan P.; Adrain, Colin; Lüthi, Alexander U.; Dominguez, Mariana Ribeiro; Yon, Monica; Barrence, Fernanda C; Riul, Thalita Bachelli; Cummings, Richard D.; Zorn, Telma Maria Tenório; Amigorena, Sébastian; Dias‐Baruffi, Marcelo; Rodrigues, Maurício M.; Martin, Séamus J.; Rabinovich, Gabriel A.; Amarante-Mendes, Gustavo P.

doi:10.1038/cddis.2017.506

Cited by 24 publications

(20 citation statements)

References 40 publications

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“…PIBF inhibits NK cell degranulation, while recent studies revealed the ability of Gal‐1 to control the non‐secretory lytic pathway of cytotoxic cells, by influencing Fas‐Fas ligand interactions …”

Section: Discussionmentioning

confidence: 99%

The involvement of the progesterone receptor in PIBF and Gal‐1 expression in the mouse endometrium

Mulac‐Jeričević

Šućurović

Gulić

et al. 2019

American J Rep Immunol

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Problem The progesterone‐regulated genes, PIBF and Gal‐1, are key players in the feto‐maternal immunological interaction. This study aims to investigate the expression of PIBF and Gal‐1 in WT and progesterone receptor KO models as well as subsequent effects of PIBF on decidualization of stromal cells. Method of the study PRAKO, PRBKO and PRKO BALB/c mice were used for assessing the role of PR isoforms in PIBF induction. PIBF‐ and Gal‐1 mRNA expression in the uterus was tested by real‐time PCR. The effect of PIBF on decidualization of endometrial stromal cells was verified by anti‐desmin immunofluorescence. Immunohistochemistry was used for testing PIBF expression in the uterus. Gal‐1, ERα and PR positive decidual NK cells were detected by immunofluorescence. Results PIBF mRNA was significantly increased in progesterone‐treated WT mice, but not in PRKO and PRAKO mice. PIBF protein expression was reduced in the endometria of PRKO and PRAKO, but not in PRBKO mice. During a 6‐day culture, PIBF induced decidual transformation of endometrial stromal cells. PIBF expression in the mouse uterus was highest during the implantation window, while Gal‐1 mRNA expression continuously increased between day 2.5 and day 11.5 of gestation. Decidual NK cells express Gal‐1 and ERα, but not PR at day 7.5 murine pregnancy. Conclusion PIBF produced via engagement of PRA, is highly expressed in the endometrium during the implantation window, and plays a role in decidualization. The concerted action of PIBF and Gal‐1 might contribute to the low cytotoxic activity of decidual NK cells.

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Section: Discussionmentioning

confidence: 99%

The involvement of the progesterone receptor in PIBF and Gal‐1 expression in the mouse endometrium

Mulac‐Jeričević

Šućurović

Gulić

et al. 2019

American J Rep Immunol

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“…68 In T cells, it is controlling T cell effector function homeostasis by regulating activation, differentiation, survival and cytokine production. 69 Galectin-1 is known to be a pro-tumorigenic and proangiogenic factor in cancer progression and has been associated with immune disorders such as HIV. 82 Overexpression of Galectin-1 was observed to be linked to progression of many types of cancers, including osteosarcoma, breast, lung and prostate cancers and in melanoma.…”

Section: Galectinsmentioning

confidence: 99%

“…Cancer immunotherapies targeting the interaction of human T cells with tumor cells by use of agents that bind to glycans or glycan binding proteins Many studies have aimed to induce specific immune responses against tumor-associated glycans and glycoproteins. 86 For • Induction of tolerogenic signaling and immune suppression 68,69 PRO…”

Section: Targeting the Tumor Or T Cell Glycome For Therapeutic Purposesmentioning

confidence: 99%

Human T cell glycosylation and implications on immune therapy for cancer

Bousser

Meuris

Callewaert

et al. 2020

Human Vaccines & Immunotherapeutics

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Glycosylation is an important post-translational modification, giving rise to a diverse and abundant repertoire of glycans on the cell surface, collectively known as the glycome. When focusing on immunity, glycans are indispensable in virtually all signaling and cell-cell interactions. More specifically, glycans have been shown to regulate key pathophysiological steps within T cell biology such as T cell development, thymocyte selection, T cell activity and signaling as well as T cell differentiation and proliferation. They are of major importance in determining the interaction of human T cells with tumor cells. In this review, we will describe the role of glycosylation of human T cells in more depth, elaborate on the importance of glycosylation in the interaction of human T cells with tumor cells and discuss the potential of cancer immunotherapies that are based on manipulating the glycome functions at the tumor immune interface.

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“…The main mechanism of cytotoxicity used by CD8+ T cells is the degranulation of granzymes and perforin, causing apoptosis in the target cells [98]. A component associated with the killing of tumor cells by CD8+ T cells is Galectin-1, which has been implicated as part of the cytotoxic granule machinery [99]. This molecule has been already described as a regulator of the CD8+ T cell expansion in vivo [100], which can eliminate antigenspecific targets in vivo [101] by acting through the Fas/FasL axis [102].…”

Section: Cancer Vaccinesmentioning

confidence: 99%