The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect DOI Open Access

Xiaoqun Guan,

Hope Fury, Priya D. Issuree

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 280 - 280

Опубликована: Дек. 31, 2024

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity driven by donor T cells, it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that colonization of mice with helminths preserves response while suppressing GVHD. As helper-2 (Th2) pathway critical helminthic regulation, we asked whether genetic induction Th2 signaling in cells regulation after BMT. Our studies utilized transgenic lymphocytes overexpress a constitutively active form Th2-associated transcription factor STAT6. Constitutively STAT6 sustained without causing severe acute GVHD, where generated robust quantities cytotoxic proteins important such as granzymes A B, interferon-γ Fas ligand, addition generating high Th2/regulatory cytokines. Bioinformatic analysis based on chromosome precipitation experiments indicated stimulates expression directly. Thus, preserving GVHD mortality, our results indicate therapeutic potential restoring modulation targeting STAT6-dependent cell maturation.

Язык: Английский

Type 2 immunity in allergic diseases DOI Creative Commons
İsmail Öğülür, Yasutaka Mitamura,

Duygu Yazıcı

и другие.

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Язык: Английский

Процитировано

21
Malignant JAK-signaling: at the interface of inflammation and malignant transformation DOI Creative Commons
Florian Perner, Heike L. Pahl, Robert Zeiser

и другие.

Leukemia, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Abstract The JAK pathway is central to mammalian cell communication, characterized by rapid responses, receptor versatility, and fine-tuned regulation. It involves Janus kinases (JAK1, JAK2, JAK3, TYK2), which are activated when natural ligands bind receptors, leading autophosphorylation activation of STAT transcription factors [1, 2]. JAK-dependent signaling plays a pivotal role in coordinating communication networks across broad spectrum biological systems including development, immune growth, differentiation. JAKs frequently mutated the aging hematopoietic system [3, 4] cancers [5]. Thus, dysregulation results various diseases, disorders. binding extracellular class I II cytokine receptors initiates critical cascade through (JAKs). Upon ligand engagement, become phosphorylate specific tyrosine residues on receptor, creating docking sites for signal transducer activator (STAT) proteins. Subsequent JAK-mediated phosphorylation STATs enables their dimerization nuclear translocation, where they function as modulate gene expression. Under physiological conditions, JAK-signaling tightly regulated mechanism that governs cellular responses external cues, such cytokines growth factors, ensuring homeostasis maintaining functional integrity tissues organs. Highly defined regulation essential balancing inflammatory stimuli signals, thus safeguarding tissue health. In contrast, dysregulated chronic inflammation unrestrained proliferation associated with diseases. Understanding qualitative quantitative differences at interface physiologic its aberrant disease crucial development targeted therapies precisely tune this target pathologic patterns while leaving homeostatic processes largely unaffected. Consequently, pharmaceutical research has drug approval several substances different selectivity profiles towards individual JAKs. Yet, precise impact inhibitor complex interplay modules within normal malignant cells remains incompletely understood. review, we summarize current knowledge health highlight recent advances future directions field.

Язык: Английский

Процитировано

3
STAT6 mutations compensate for CREBBP mutations and hyperactivate IL4/STAT6/RRAGD/mTOR signaling in follicular lymphoma DOI Creative Commons
Qing Shao, Karan Bedi,

I. Malek

и другие.

Leukemia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Activating mutations in STAT6 are common Follicular Lymphoma (FL) and transformed FL various other B cell lymphomas. Here, we report RNA-seq based gene expression data on normal human lymph node derived lymphocytes (NBC; N = 6), primary WT ( 11) or mutant 4) for before after ex vivo stimulation with IL4. We found that mutants result broad augmentation of IL4-induced expression. Unexpectedly, measured reduced baseline levels when compared NBC mutations. tracked the attenuated IL4/JAK/STAT6 response to co-existing CREBBP experimentally verified intact is required induction many genes. One genes here identified RRAGD , a small G-protein involved lysosomal mTOR activation. show IL4 treatment induced expression, activation lymphoma cells IL4-enhanced BCR signaling The BCR-induced was by augmented STAT6, establishing link between regulated pro-growth pathways lymphoma.

Язык: Английский

Процитировано

1
The genetics of hyper IgE syndromes DOI Creative Commons

Randa S AlYafie,

Dinesh Velayutham, Nicholas van Panhuys

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 18, 2025

Hyper IgE syndromes (HIES) form a rare group of primary immunodeficiency disorders (PIDs) distinguished by persistent skin abscesses, dermatitis, allergies, and infections, in addition to their characteristic high serum levels. Autosomal dominant (AD) autosomal recessive (AR) genetic defects have been reported HIES. From clinical perspective, AD-HIES cases generally exhibit several non-immunologic features, including connective tissue, dental skeletal abnormalities, whilst AR-HIES conditions higher incidence neurologic complications cutaneous viral infections. Genetic associated with HIES lead impaired immune signaling, affecting pathways crucial for cell development, function, response pathogens/allergens. As result, patients are predisposed recurrent bacterial and/or fungal as well atopic allergic responses. In many cases, the exact biological mechanisms responsible variations observed phenotypes between two inherited forms still unclear. this review, we describe basis distinction forms, better comprehend different underlying molecular mechanisms, which is imperative accurate diagnosis, management, development targeted therapies patients.

Язык: Английский

Процитировано

1
Efficacy and safety analysis of Dupilumab for atopic dermatitis of all ages in Chinese population: Real‐world data from a single center DOI
Zijing Yang,

Wanting Wen,

Ruofei Shi

и другие.

Allergy, Год журнала: 2024, Номер 79(5), С. 1379 - 1382

Опубликована: Фев. 29, 2024

The data that supports the findings of this study are available in supplementary material article. Tables S1–S4. Please note: publisher is not responsible for content or functionality any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author

Язык: Английский

Процитировано

5
Rapid identification of primary atopic disorders (PAD) by a clinical landmarkguided, upfront use of genomic sequencing DOI
Tim Niehues, Sandra von Hardenberg, Eunike Velleuer

и другие.

Allergologie select, Год журнала: 2024, Номер 8(01), С. 304 - 323

Опубликована: Янв. 1, 2024

Primary atopic disorders (PAD) are monogenic caused by pathogenic gene variants encoding proteins that key for the maintenance of a healthy skin barrier and well-functioning immune system. Physicians face challenge to find single, extremely rare PAD patients/families among millions individuals with common allergic diseases. We describe case scenarios signature PAD. review literature deduct specific clinical red flags detection. They include positive family history and/or signs pathological susceptibility infections, immunodysregulation, or syndromic disease. Results conventional laboratory most immunological lab studies not sufficient make definitive diagnosis In past, multistep narrowing differential diagnoses various other tests led testing single genes panel analyses, which was time-consuming often unsuccessful approach. The implementation whole-genomic analyses in routine diagnostics has paradigm shift. Upfront genome-wide analysis whole genome sequencing (WGS) will shorten time diagnosis, save patients from unnecessary investigations, reduce morbidity mortality. propose rational, landmark-based approach deciding cases pass filter carrying out early WGS. WGS result interpretation requires great deal caution regarding causal relationship phenotypes absence proof adequate functional tests. negative results, re-iteration attitude re-analyses data (using latest base annotation)) may eventually lead diagnosis. PAD, like many genetic diseases, only be successfully managed, if physicians different specialties geneticists interact regularly multidisciplinary conferences.

Язык: Английский

Процитировано

5
Primary atopic disorders: inborn errors of immunity causing severe allergic disease DOI Creative Commons
Maryam Vaseghi‐Shanjani, Simran Samra, Pariya Yousefi

и другие.

Current Opinion in Immunology, Год журнала: 2025, Номер 94, С. 102538 - 102538

Опубликована: Фев. 27, 2025

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and food allergies, are driven by dysregulated immune responses, often involving IgE-mediated mast cell basophil activation, Th2 inflammation, epithelial dysfunction. While environmental factors well-known contributors, the genetic components underpinning these conditions increasingly understood. Traditionally viewed as polygenic multifactorial disorders, diseases can also be caused single-gene defects affecting system skin barrier, leading to profoundly responses. These monogenic disorders collectively referred primary or PADs. To date, over 48 have been established cause This review highlights (i) significance of PADs, (ii) biological pathways involved in pathogenesis (iii) clinical strategies differentiate PADs from their much more common counterparts, (iv) diagnostic for

Язык: Английский

Процитировано

0
Atopic dermatitis and lymphoma risk: a systematic review and meta-analysis DOI Creative Commons
Yingjie Tian,

Yujin Li,

Chen Yang

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 14, 2025

Background The relationship between atopic dermatitis (AD) and lymphoma risk remains debate. This study systematically evaluates in AD patients compared to non-AD individuals. Methods A systematic search of PubMed, Embase, the Cochrane Library (up August 11, 2024) identified observational studies reporting estimates for patients. Pooled odds ratios (OR) or relative risks (RR) with 95% CIs were calculated using a random-effects model (PROSPERO ID: CRD42024577019). Results Of 2,366 articles screened, 13 met inclusion criteria. was significantly associated elevated (OR = 2.56, CI: 1.75–3.74, P < 0.001; RR 1.23, 1.15–1.31, 0.001). increased severity, severe cases showing highest effect size (RR 2.63; 1.94–3.58, OR 2.60; 1.71–3.96, Subgroup analyses revealed high Hodgkin (HL) 1.54, 1.35–1.75, 0.001) non-Hodgkin 1.15, 1.04–1.28, 0.006). Notably, T-cell (TCL) showed 4.25; 1.94–9.33, whereas no significant association observed B-cell 1.07; 0.95–1.20, 0.271). Conclusion is risk, particularly HL, NHL TCL. severity may amplify this risk. Future research warranted explore underlying mechanisms address limitations current evidence. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024577019.

Язык: Английский

Процитировано

0
Generation and functional characterization of tuft cells in non-human primate pancreatic ducts through organoid culture systems DOI Creative Commons
Kazushige Sakaguchi, Chiemi Nakajima,

Akihiko Inaba

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Май 6, 2025

The pancreatic duct plays a key role in collecting juice, which is rich digestive enzymes. fluid flows unidirectionally into the duodenum, where it mixes with partially digested food to further facilitate digestion. In this study, we report generation of ductal organoids from non-human primates for first time, aimed at investigating tuft cells that reside since no studies have addressed pancreas. were maintained medium supplemented Wnt3a, Noggin, R-spondin, and other factors support proliferation. These expressed stem cell marker LGR5 mRNA protein CK19, although markers not detectable stage. Upon stimulation IL-4/13, differentiation was confirmed by immunohistochemistry transcriptomic analysis. We observed induction DCLK1, as well taste signaling molecules such TRPM5 PLCβ2, are type II cells. Additionally, upregulation LYZ DEFB1 indicated expression antimicrobial peptide markers, alongside associated inflammation. Furthermore, differentiated specifically responded bitter compound, suggesting may play detecting potentially harmful chemicals. Finally, immunohistochemical analysis identified primate pancreas, supporting their involvement sensing compounds regulating protective responses within

Язык: Английский

Процитировано

0
Association of STAT6 Gene Polymorphism with Atopic Asthma among Yemeni Children in Sana'a City, Yemen DOI

Haitham Abdulwahab Masood,

Arwa Mohammed Othman,

Najla Nasr Addin Al-Sonboly

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Background Asthma is the most common chronic illness in children and characterized by airway hyperresponsiveness, increased production of mucus, significant inflammation. The signal transducer activator transcription 6 (STAT6) a crucial gene immune response, specifically atopic reactions. It plays role IL-4 IL-13 signaling pathways asthma allergies. Objective This study aimed to determine association between STAT6 rs324011 polymorphism among Yemeni as well investigate impact on IL-13, total IgE, eosinophils. Methods included 75 diagnosed with bronchial healthy controls matched for age sex. (rs324011) was genotyped using RFLP PCR, serum level measured via ELISA, IgE electrochemiluminescence. Results Under recessive model, TT genotype significantly associated an risk compared CC CT genotypes (χ2 = 6.6, OR = 2.5, CI 1.2–5, p 0.01). levels asthmatic were elevated individuals those or (p=0.04). Conclusion T allele may be susceptibility pediatric children.

Язык: Английский

Процитировано

0