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Dynamic P-glycoprotein expression in early and late memory states of human CD8 + T cells and the protective role of ruxolitinib.
Biomed Pharmacother
January 2025
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary; Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen 4032, Hungary; Dean's office, Faculty of Pharmacy, University of Debrecen, Debrecen 4032, Hungary. Electronic address:
ABCB1/MDR-1/P-glycoprotein (Pgp) is an ABC transporter responsible for cancer cell multi-drug resistance. It is expressed in cytotoxic T lymphocytes (CTL). Eliminating sensitive cancer cells during high-dose chemotherapy can also damage immune cells.
View Article and Find Full Text PDFIFN-γ-producing T1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren's disease.
Sci Transl Med
December 2024
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous.
View Article and Find Full Text PDFCo-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia.
Leukemia
December 2024
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach.
View Article and Find Full Text PDFRuxolitinib-dependent reduction of seizure load and duration is accompanied by spatial memory improvement in the rat pilocarpine model of temporal lobe epilepsy.
Neurotherapeutics
December 2024
Department of Neurology, University of California Davis School of Medicine, Sacramento, CA, USA. Electronic address:
Molecules with optimized pharmacokinetic properties selectively aimed at the inhibition of STAT3 phosphorylation in brain have recently emerged as potential disease modifying therapies for epilepsy. In the current study, pharmacological inhibition of JAK1/2 with the orally available, FDA-approved drug ruxolitinib, produced nearly complete inhibition of hippocampal STAT3 phosphorylation, and reduced the expression of its downstream target Cyclin D1, when administered to rats 30 ​min and 3 ​h after onset of pilocarpine-induced status epilepticus (SE). This effect was accompanied by significantly shorter seizure duration and lower overall seizure frequency throughout the 4 weeks of EEG recording, but did not completely prevent the development of epilepsy in ruxolitinib-treated male rats.
View Article and Find Full Text PDFType 2 cytokine-JAK1 signaling is involved in the development of dry skin-induced mechanical alloknesis.
J Dermatol Sci
October 2024
Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan. Electronic address:
Background: Mechanical alloknesis (m-alloknesis) is itch hypersensitivity induced by normally innocuous stimuli. It is sometimes observed in dry skin based itch-related diseases such as atopic dermatitis (AD), and often triggers the vicious itch-scratch cycle. The acetone-ether and water (AEW) mouse model mimics dry skin-induced m-alloknesis, yet its underlying mechanism remains unclear.
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