Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4+ and CD8+ T Cells and Counteracts the Induction of Type 1 Regulatory T Cells

Jasiecka-Mikołajczyk, Agnieszka; Jaroszewski, Jerzy Jan; Maślanka, Tomasz

doi:10.3390/molecules26185655

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…IL-27 was diluted in 1% bovine serum albumin (BSA; carrier protein; Sigma-Aldrich) in phosphate buffered saline (PBS; Dulbecco’s PBS devoid of Ca 2+ and Mg 2+ ; Sigma-Aldrich); therefore, the same amount of % BSA in PBS was added to control and TER- and ATRA-treated cells. Cells were stimulated similarly as in our previous works [ 78 , 79 ] and others’ works [ 80 , 81 , 82 ]. Briefly, cells were activated for 72 h with plate-coated anti-CD3 (Purified NA/LE hamster anti-mouse CD3e, 1 μg/mL, clone 145-2C11) and soluble anti-CD28 (Purified NA/LE hamster anti-mouse CD28, 1 μg/mL, clone 37.51) in the presence of IL-2 (Recombinant mouse IL-2, 20 ng/mL; all reagents from BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4+ T Regulatory T Cells—An In Vitro Study

Maślanka¹

2022

Molecules

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The principal goal of the study was to verify the concept of pharmacological induction of Foxp3+CD25+CD4+ T regulatory (Treg) cells which will additionally be characterized by a highly suppressive phenotype, i.e., by extensive CD25 and CD39 expression and IL-10 and TGF-β production. Stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER), and all trans retinoic acid (ATRA) alone and to their combinations. The study demonstrated that: (a) IL-27 alone induced CD39 expression on Treg cells and the generation of Tr1 cells; (b) TER alone induced Foxp3-expressing CD4+ T cells and up-regulated density of CD25 on these cells; TER also induced the ability of Treg cells to TGF-β production; (c) ATRA alone induced CD39 expression on Treg cells. The experiments revealed a strong superadditive effect between IL-27 and ATRA with respect to increasing CD39 expression on Treg cells. Moreover, IL-27 and ATRA in combination, but not alone, induced the ability of Treg cells to IL-10 production. However, the combination of IL-27, TER, and ATRA did not induce the generation of Treg cell subset with all described above features. This was due to the fact that TER abolished all listed above desired effects induced by IL-27 alone, ATRA alone, and their combination. IL-27 alone, ATRA alone, and their combination affected TER-induced effects to a lesser extent. Therefore, it can be concluded that in the aspect of pharmacological induction of Treg cells with a highly suppressive phenotype, the triple combination treatment with TER, IL-27, and ATRA does not provide any benefits over TER alone or dual combination including IL-27 and ATRA.

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Section: Methodsmentioning

confidence: 99%

Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4+ T Regulatory T Cells—An In Vitro Study

Maślanka¹

2022

Molecules

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“…In cases of dermatitis, blockade of histamine receptors using thioperamide or JNJ7777120 decreased hapten-induced local inflammation and IL-13 secretion by CD8 T cells, with a more pronounced inhibitory effect than that of CD4 T cells 69 . Oclacitinib, a Janus kinase inhibitor indicated for pruritus or atopic dermatitis in dogs 178 , has shown a significant reduction in Tc2 and Th2 cells, and this treatment effect was more pronounced for Tc2 cells than for Th2 cells 179 . Allergen immunotherapy, another potential strategy, has been shown to significantly reduce the intracellular expression of IL-4 by Tc2 cells in the context of intermittent allergic rhinitis 64 .…”

Section: Therapeutic Potential Of Tc Subsetsmentioning

confidence: 99%

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Koh,

Lee,

Kwak

et al. 2023

Exp Mol Med

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CD8 T cells play crucial roles in immune surveillance and defense against infections and cancer. After encountering antigenic stimulation, naïve CD8 T cells differentiate and acquire effector functions, enabling them to eliminate infected or malignant cells. Traditionally, cytotoxic T cells, characterized by their ability to produce effector cytokines and release cytotoxic granules to directly kill target cells, have been recognized as the constituents of the predominant effector T-cell subset. However, emerging evidence suggests distinct subsets of effector CD8 T cells that each exhibit unique effector functions and therapeutic potential. This review highlights recent advancements in our understanding of CD8 T-cell subsets and the contributions of these cells to various disease pathologies. Understanding the diverse roles and functions of effector CD8 T-cell subsets is crucial to discern the complex dynamics of immune responses in different disease settings. Furthermore, the development of immunotherapeutic approaches that specifically target and regulate the function of distinct CD8 T-cell subsets holds great promise for precision medicine.

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“…Our earlier study strongly suggests that this depletive effect of OCL is more likely to be responsible for the proapoptotic effect of the drug than its antiproliferative effect (Jasiecka-Mikołajczyk et al 2018, 2021. This is also implies by results of other research, in which it was demonstrated that that OCL did not significantly affect T cells proliferation (Banovic et al 2019).…”

Section: Discussionmentioning

confidence: 56%

“…The main mechanism of OCL action rely on the inhibition of cytokine-mediated signaling via blockade of the JAK-STAT signaling pathway. However our previous studies found that the drug may have a more complex mechanism of action (Jasiecka-Mikołajczyk et al 2021). Considering the fact that T and B cells are involved in the pathophysiology of AD in dogs (Olivry et al 1999, Nuttall et al 2002, Schlotter et al 2011, Majewska et al 2022, the depletive effect of the drug toward these cells may contribute to the beneficial effects of OCL in the treatment of skin allergic diseases.…”

Section: Discussionmentioning

confidence: 99%

Depletion of T and B cells in lymphoid tissues of mice induced by oclacitinib, a Janus kinase inhibitor

Jasiecka-Mikołajczyk,

Maślanka

2023

Polish Journal of Veterinary Sciences

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The main purpose of the study was to determine the safety of oclacitinib (OCL), a Janus kinase inhibitor, with respect of its effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. The mice were treated orally with OCL at a dose of 2.7 mg/kg for 14 days and peripheral blood, head and neck lymph nodes (HNLNs), mediastinal lymph nodes (MLNs) and spleen were collected. The study found that OCL induced depletion of CD4 + T cells in the HNLNs and MLNs, while it did not affect the absolute count of CD8 + T cells in these tissues. Also OCL caused a loss of B cells in the HNLNs, although not in the MLNs. Moreover, OCL depleted B cells in the peripheral blood, but did not affect the absolute count of CD4 + and CD8 + T cells. Thus, it can be concluded that OCL may induce a depletive effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. This effect should be seen as an unfavorable one, especially in patients with infections. Therefore, a clinical implication is that in such patients, the benefit/risk ratio should be thoroughly considered by clinicians. Moreover, OCL reduced the absolute count of eosinophils, basophils, neutrophils and monocytes. However, it is uncertain whether this effect should be considered to be of clinical importance because the levels of these cells were within the physiological range. It is possible that the depletive effect of OCL toward T and B cells, as well as eosinophils and basophils may contribute to the beneficial effects of the drug in the treatment of skin allergic diseases.

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Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4+ and CD8+ T Cells and Counteracts the Induction of Type 1 Regulatory T Cells

Cited by 8 publications

References 45 publications

Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4+ T Regulatory T Cells—An In Vitro Study

Effect of IL-27, Teriflunomide and Retinoic Acid and Their Combinations on CD4+ T Regulatory T Cells—An In Vitro Study

CD8 T-cell subsets: heterogeneity, functions, and therapeutic potential

Depletion of T and B cells in lymphoid tissues of mice induced by oclacitinib, a Janus kinase inhibitor

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