TGF-  downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients

Crane, Courtney A.; Han, Seunggu J.; Barry, Jeffery J.; Ahn, Brian; Lanier, Lewis L.; Parsa, Andrew T.

doi:10.1093/neuonc/nop009

Cited by 264 publications

(221 citation statements)

References 17 publications

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“…of lymphocytes [36,37]. We observed a significant reduction in the expression level of the activating NKR-P1A receptor compared to control after 4 days of culture in the presence of TGF-β1.…”

Section: Nkr-p1 Receptor Expression Is Modulated By Cytokinesmentioning

confidence: 84%

“…Presence of IL-15 sustained growth and viability of the NK cells but did not induce any differences in the expression levels of NKR-P1 receptors. The anti-inflammatory cytokine TGF-β1 is known to reduce the expression of several NK-receptors and reduce functionality Organs from several animals were pooled at each time point (day 0: n = 7, 3 w: n = 3, 10 w: n = 2) and data shown are from one experiment representative of two independent experiments performed.of lymphocytes [36,37]. We observed a significant reduction in the expression level of the activating NKR-P1A receptor compared to control after 4 days of culture in the presence of TGF-β1.…”

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confidence: 99%

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Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca 2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A + T cells in all tissues analyzed, and by many NKR-P1A − intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A + and NKR-P1F + cells was high at birth and thereafter declined, while NKR-P1B + and NKR-P1G + cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.Keywords: C-type lectin-related molecules r NK-cell receptors r NKR-P1 r Rodent Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNatural killer (NK) cells are innate lymphoid cells with the ability to eliminate virally infected cells and transformed or allogeneic cells. They produce cytokines early in the immune response, and play an important role in shaping the immune response, e.g. in the context of inflammation and transplantation. These tasks are controlled by a wide range of receptors with different functions and ligands, such as Ly49 receptors, which recognize both classical and nonclassical MHC class I molecules, as well as MHC Correspondence: Dr. Lise Kveberg e-mail: lise.kveberg@rr-research.no class I-like virally encoded ligands [1][2][3]. Another family of MHCbinding receptors is the conserved NKG2/CD94 heterodimers, which bind the nonclassical MHC molecule HLA-E in human [4], its rodent homologue Qa-1 b in the mouse [5,6] and RT.BM1 in the rat [7]. Both the Ly49 and NKG2/CD94 receptor families contain inhibitory and activating members. NKG2D is a promiscuous activating receptor, recognizing several MHC class I-related ligands frequently upregulated upon cellular stress and associated with viral infection and malignant transformation [8].The activating NK cytotoxicity receptors react with several virus-derived and endogenous ligands [9,10].One of the earliest NK-cell receptors to be characterized was the NK-cell receptor protein 1A (NKR-P1A) in the rat, which is C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 502Lise Kveberg et al. Eur. J. Immunol. 2015. 45: 501-...

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Section: Nkr-p1 Receptor Expression Is Modulated By Cytokinesmentioning

confidence: 84%

mentioning

confidence: 99%

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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“…Additionally, TGF-b expressed by T cells may inhibit proliferation of NK cells in vivo after they become activated by infection with acute lymphocytic choriomeningitis virus (LCMV) (Su et al 1991(Su et al , 1993, or by hepatitis B virus (HBV) infection in humans (Sun et al 2012). NK cells express activating receptors at their surface, including NKG2D and NKp30, whose expression is suppressed by TGF-b (Castriconi et al 2003;Lee et al 2004;Crane et al 2010). The expression of NKG2D at the cell surface requires its association with the intracellular adaptors DAP10 or DAP12 to stabilize the complex.…”

Section: Nk Cellsmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

448

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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“…Several factors could mediate this effect on NK cell functions. The plasma levels of anti-inflammatory molecules, such as TGF-b, were shown to be elevated in the context of brain tumors and could inhibit NK cell functions, as well as the level of expression of the activating receptor NKG2D (24). Thus, decreased expression of NKG2D was shown on NK cells that were isolated from GBM patients (24).…”

Section: Nk Cell Modifications Associated With Cns Disordersmentioning

confidence: 99%

NK Cells in Central Nervous System Disorders

Poli

Kmiecik

Domingues

et al. 2013

The Journal of Immunology

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NK cells are important players in immunity against pathogens and neoplasms. As a component of the innate immune system, they are one of the first effectors on sites of inflammation. Through their cytokine production capacities, NK cells participate in the development of a potent adaptive immune response. Furthermore, NK cells were found to have regulatory functions to limit and prevent autoimmunity via killing of autologous immune cells. These paradoxical functions of NK cells are reflected in CNS disorders. In this review, we discuss the phenotypes and functional features of peripheral and brain NK cells in brain tumors and infections, neurodegenerative diseases, acute vascular and traumatic damage, as well as mental disorders. We also discuss the implication of NK cells in neurotoxicity and neuroprotection following CNS pathology, as well as the crosstalk between NK cells and brain-resident immune cells.

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TGF- downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients

Cited by 264 publications

References 17 publications

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

NK Cells in Central Nervous System Disorders

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