Dataset Information

Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.

ABSTRACT: NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus-infected cells. Given the vast diversity of receptors expressed on NK cells we seek to identify receptors involved in the recognition of HIV-1-infected cells. By combining an unbiased large-scale screening approach with a functional assay, we identify TRAIL to be associated with NK cell degranulation against HIV-1-infected target cells. Further investigating the underlying mechanisms, we demonstrate that TRAIL is able to elicit multiple effector functions in human NK cells independent of receptor-mediated induction of apoptosis. Direct engagement of TRAIL not only results in degranulation but also IFNγ production. Moreover, TRAIL-mediated NK cell activation is not limited to its cognate death receptors but also decoy receptor I, adding a new perspective to the perceived regulatory role of decoy receptors in TRAIL-mediated cytotoxicity. Based on these findings, we propose that TRAIL not only contributes to the anti-HIV-1 activity of NK cells but also possesses a multifunctional role beyond receptor-mediated induction of apoptosis, acting as a regulator for the induction of different effector functions.

SUBMITTER: Hofle J

PROVIDER: S-EPMC9346491 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.

Höfle Johannes J Trenkner Timo T Kleist Nadja N Schwane Vera V Vollmers Sarah S Barcelona Bryan B Niehrs Annika A Fittje Pia P Huynh-Tran Van Hung VH Sauter Jürgen J Schmidt Alexander H AH Peine Sven S Hoelzemer Angelique A Richert Laura L Altfeld Marcus M Körner Christian C

EMBO reports 20220627 8

NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus-infected cells. Given the vast diversity of receptors expressed on NK cells we seek to identify receptors involved in the recognition of HIV-1-infected cells. By combining an unbiased large-scale screening approach with a functional assay, we identify TRAIL to be associated with NK cell degranulation against HIV-1-infected target cells. Further investigating the underlying mechanisms, we demonstrate th ...[more]

PMID: 35758160

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Project description:Graves' disease (GD) is an autoimmune disorder, driven by the appearance of circulating autoantibodies (Ab) against the thyroid stimulating hormone (TSH) receptor, thus causing hyperthyroidism. While antithyroid drugs, the only available treatment for GD, carry a significant risk of relapse, advances in immunology could pave the way for more effective therapies. Natural killer (NK) cells, divided into cytotoxic CD56dim and cytokine-secreting CD56bright subsets, regulate immune responses through cytokine production and cell lysis and may play a role in the pathogenesis of GD. To investigate their involvement, we conducted flow cytometry on peripheral blood samples from 131 GD patients at various stages (disease onset, on antithyroid drugs, and in remission) and 97 age- and sex-matched healthy controls (HC). We analyzed NK cell subsets, activating (CD16, CD69, NKG2D, NKp30) and inhibitory receptors (CD161, NKG2A), degranulation (CD107a), and intracellular cytokines expression (interferon γ, tumor necrosis factor α). Statistical comparisons were made between GD patients and HC and across disease stages. GD patients had a higher frequency of total NK cells (p < 0.028) and CD56bright NK cells (p < 0.01) but a lower frequency of CD56dim NK cells (p = 0.005) compared to HC. NK cells in GD patients expressed activating receptors more frequently, except for NKG2D, but had decreased cytokine expression and degranulation ability. At GD onset, patients had higher frequencies of total NK cells, CD56bright NK cells, and NK cells expressing activating receptors compared to patients receiving ATD treatment and those in remission. CD161+ NK cells were lower at GD onset and returned to levels of HC following treatment. Correlation analysis revealed that free thyroxine (FT4) levels were inversely correlated with CD107a+ NK cells (p < 0.05) and positively correlated with CD69+ NK cells (p < 0.01). These findings suggest that hyperthyroidism impairs NK cell degranulation, with the increased frequency of NK cells potentially compensating for their reduced function. This dysfunction may contribute to the unregulated immune response in GD, highlighting NK cells as a potential target for novel therapeutic strategies.

Dataset Information

Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.

Publications

Engagement of TRAIL triggers degranulation and IFNγ production in human natural killer cells.

Similar Datasets

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