Common gamma chain cytokines promote regulatory T cell development and survival at the <scp>CD</scp>4<sup>+</sup> <scp>CD</scp>8<sup>+</sup> stage in the human thymus

Vanhanen, Reetta; Tuulasvaara, Anni; Mattila, Joonatan; Pätilä, Tommi; Arstila, T. Petteri

doi:10.1111/sji.12681

Cited by 9 publications

(8 citation statements)

References 34 publications

(93 reference statements)

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“…Future work should try to determine whether this ex vivo finding has relevance within the fish thymus, try to discover where in the fish thymus IL-2 is expressed, and investigate whether the fish DP population can be divided into IL-2 responding and non-responding populations. Possibly, the IL-2-sensitive DP thymocytes are T reg cells expressing relatively high levels of IL-15Rα [see mammalian study (89)], but antibodies against trout IL-15Rα which could help investigate this matter are not yet available.…”

Section: Discussionmentioning

confidence: 99%

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

et al. 2020

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Related interleukin-2, -15, and -15-like (IL-2, -15, and -15L) are ancient cytokines, with all three genes surviving in extant fish and some mammals. The present study is the first to identify IL-15L functions, namely in rainbow trout. In isolated trout splenocytes, and in vivo, purified recombinant IL-15L+IL-15Rα molecules induced expression of IL-4 and IL-13 homologs, which are markers of type 2 immunity. In contrast, trout IL-15 stimulated type 1 immunity markers, thus IL-15 and IL-15L can have opposing functions. Trout IL-15L was more dependent on "in trans" presentation by the receptor chain IL-15Rα than IL-15, and stimulated CD4 − CD8 − (IgM − ) lymphocytes from thymus and spleen. We propose an important role for IL-15L early in the type 2 immunity cytokine cascade. Trout IL-2 and IL-15 exhibited features reminiscent of their mechanistic and functional dichotomy observed in mammals; for example, IL-15 but not IL-2 required a receptor alpha chain (only IL-15Rα in the case of fish) for its stability, and only IL-15 was efficient in stimulating lymphocytes from mucosal tissues. Data suggest that IL-15L and IL-15 may be particularly effective in stimulating innate lymphocyte type 2 cells (ILC2) and natural killer (NK) cells, respectively, but further identification of the cell types is needed. An interesting finding different from in mammals was the efficient stimulation of CD4 + CD8 + thymocytes by IL-2. In short, this study presents fundamental information on the evolution of the IL-2/15/15L cytokine family.

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Section: Discussionmentioning

confidence: 99%

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

et al. 2020

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“…Indeed, the proliferation history of End#6 cells (both CD8 neg and CD8 dim ) showed many more cell divisions than any other thymic subset, more than naive T cells in the periphery (by a measured dilution of TREC DNA in the sorted subsets). Our End#6 CD8 dim population may have been included in the FOXP3 pos DP cells placed at the beginning of Treg development in previous studies ( 39,69 ). Our approach provides a tool which can overcome the limitations of conventional gating and help to distinguish these cells.…”

Section: Discussionmentioning

confidence: 99%

Deconstructing Complexity: A Computational Topology Approach to Trajectory Inference in the Human Thymus withtviblindi

Stuchly,

Novak,

Brdickova

et al. 2023

Preprint

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Interpreting and understanding complex, organ-level mass cytometry datasets represents a formidable interdisciplinary challenge. This study aims to identify, describe, and interpret potential developmental trajectories of thymocytes and mature T cells. We developedtviblindi, a trajectory inference algorithm that integrates several autonomous modules - pseudotime inference, random walk simulations, real-time topological classification using persistence homology, and autoencoder-based 2D visualization using thevaevictisalgorithm. This integration facilitates an interactive exploration of developmental trajectories. The utility and proficiency oftviblindiare demonstrated through comprehensive analysis of the thymic and peripheral T-cell compartment. Our approach not only uncovers and elucidates the canonical CD4 and CD8 development but also offers insights into various checkpoints such as TCRβ selection and positive/negative selection, elucidating the crossroads between further development and apoptosis. Finally, we identify and thoroughly characterize thymic regulatory T cells, tracing their development from the negative selection stage to mature thymic regulatory T cells with an extensive proliferation history and an immunophenotype of activated and recirculating cells.tviblindiis a versatile and generic approach suitable for any single-cell dataset, equipping biologists with an effective tool for interpreting complex data.

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“…IL-2 is a common cytokine in human body. CD4 + and CD8 + and T cells are important components of IL-2 and important factors in the regulation of immune function [23]. IL-2 can stimulate T cells to produce INF-γ, activating multiple immune cells [24].…”

Section: Discussionmentioning

confidence: 99%

Effect of Dexmedetomidine-Mediated Insulin-Like Growth Factor 2 (IGF2) Signal Pathway on Immune Function and Invasion and Migration of Cancer Cells in Rats with Ovarian Cancer

et al. 2019

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Background The aim of this study was to explore the effect of dexmedetomidine (DEX)-mediated insulin-like growth factor 2 (IGF2) signal pathway on immune function and cancer cell invasion and migration in rats with ovarian cancer. Material/Methods Forty rats with ovarian cancer were divided into 4 groups: model group, and low dose (0.2 μg/kg/hour DEX), medium dose (1.0 μg/kg/hour DEX), and high dose (5.0 μg/kg/hour DEX) DEX groups. In addition, 10 Fischer344 rats were selected as a normal group. Human NUTU-19 poorly differentiated epithelial ovarian cancer cell line cells were divided into 4 groups: a blank group and low dose, medium dose, and high dose DEX NUTU-19 groups. Results Compared with the normal group, in the other groups the serum interleukin (IL)-2 and interferon gamma (INF-γ) levels, CD4 + and CD8 + percentages, CD4 + /CD8 + ratio, and transformation rate of splenic lymphocytes were decreased, and the serum tumor necrosis factor alpha (TNF-α) level, IGF2, insulin-like growth factor 1 receptor (IGF1R), insulin receptor substrate 1 (IRS1) mRNA, and protein expressions in ovarian tissue were increased (all P <0.05). Results in the DEX groups compared with model group were the opposite of those in the other groups compared with normal group (all P <0.05). Compared with the blank group, in the other groups the proliferation, invasion, and migration of ovarian cancer cells were reduced significantly (all P <0.05). Compared with the low dose DEX NUTU-19 group, in the high dose DEX NUTU-19 group the invasion and migration of ovarian cancer cells weakened significantly (both P <0.05). Conclusions A certain dose of DEX can effectively inhibit IGF2 signal pathway activation to improve the immune function of rats with ovarian cancer, inhibiting the invasion and migration of ovarian cancer cells.

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Common gamma chain cytokines promote regulatory T cell development and survival at the CD4⁺ CD8⁺ stage in the human thymus

Cited by 9 publications

References 34 publications

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Deconstructing Complexity: A Computational Topology Approach to Trajectory Inference in the Human Thymus withtviblindi

Effect of Dexmedetomidine-Mediated Insulin-Like Growth Factor 2 (IGF2) Signal Pathway on Immune Function and Invasion and Migration of Cancer Cells in Rats with Ovarian Cancer

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Common gamma chain cytokines promote regulatory T cell development and survival at the CD4+ CD8+ stage in the human thymus

Cited by 9 publications

References 34 publications

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response

Deconstructing Complexity: A Computational Topology Approach to Trajectory Inference in the Human Thymus withtviblindi

Effect of Dexmedetomidine-Mediated Insulin-Like Growth Factor 2 (IGF2) Signal Pathway on Immune Function and Invasion and Migration of Cancer Cells in Rats with Ovarian Cancer

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Common gamma chain cytokines promote regulatory T cell development and survival at the CD4⁺ CD8⁺ stage in the human thymus