Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID) DOI Creative Commons
Remo Poto, Antonio Pecoraro, Anne Lise Ferrara

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 28, 2023

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID a heterogeneous disorder with presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation.In this study, we evaluated serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well lipopolysaccharide (LPS) soluble CD14 (sCD14) in individuals infectious only (INF-CVID), those additional systemic autoimmune inflammatory disorders (NIC-CVID), healthy donors (HD).Our results showed increased TNF-α, IL-6, IL-10 both INF-CVID NIC-CVID subjects compared to HD. However, elevations were significantly more marked than INF-CVID. Additionally, LPS Circulating levels sCD14 HD.These findings indicate persistent cytokine dysregulation despite IgRT CVID. Moreover, circulating profile reveals heterogeneity different subgroups subjects.

Language: Английский

TSLP, IL-33, and IL-25: Not just for allergy and helminth infection DOI Creative Commons

Alison G. Stanbery,

Shuchi Smita, Jakob von Moltke

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2022, Volume and Issue: 150(6), P. 1302 - 1313

Published: July 19, 2022

Language: Английский

Citations

50
IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications DOI Open Access
Helena Iznardo, L. Puig

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9479 - 9479

Published: Aug. 22, 2022

The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of innate immune system, linking adaptative responses. This complex composed by several cytokines, receptors, co-receptors, all working a balanced way to maintain homeostasis. Dysregulation these processes results tissue inflammation pathogenesis common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, atopic dermatitis. Therefore, therapeutic targeting IL-1 pathways has been studied, monoclonal antibodies are currently being assessed clinical trials. So far, promising have obtained with anti-IL-36R spesolimab imsidolimab pustular their efficacy tested other conditions.

Language: Английский

Citations

44
The Cytokine Network in Colorectal Cancer: Implications for New Treatment Strategies DOI Creative Commons

Heidi Braumüller,

Bernhard Mauerer,

J.C. Andri�s

et al.

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 138 - 138

Published: Dec. 29, 2022

Colorectal cancer (CRC) is one of the most frequent tumor entities worldwide with only limited therapeutic options. CRC not a genetic disease several mutations in specific oncogenes and/or suppressor genes such as APC, KRAS, PIC3CA, BRAF, SMAD4 or TP53 but also multifactorial including environmental factors. Cancer cells communicate their environment mostly via soluble factors cytokines, chemokines growth to generate favorable microenvironment (TME). The TME, heterogeneous population differentiated and progenitor cells, plays critical role regulating development, growth, invasion, metastasis therapy resistance. In this context, cytokines from TME influence each other, eliciting an inflammatory milieu that can either enhance suppress metastasis. Additionally, lines evidence exist composition microbiota regulates processes, controlled by cytokine secretion, play carcinogenesis progression. review, we discuss networks between microbiome colorectal related treatment strategies, goal cytokine-mediated strategies could overcome common resistance tumors.

Language: Английский

Citations

44
Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives DOI Creative Commons
Ashutosh Pareek, Lipika Kumari, Aaushi Pareek

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 425 - 425

Published: Feb. 28, 2024

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% children are affected by this serious condition, which painful for sufferers. Recent research has connected environment, genetics, barrier, drugs, psychological factors, and immune system to severity AD. The causes consequences AD its cellular molecular origins reviewed in paper. exploration interleukins their influence on immunological pathway been facilitated using relevant biomarkers clinical trials. This approach enables identification novel therapeutic modalities, fostering potential targeted translational within realm personalized medicine. review focuses AD’s pathophysiology ever-changing landscape. Beyond plethora biologic medications various stages approval development, a range non-biologic therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, Abrocitinib, thus expanding spectrum options. also addresses latest efficacy data elucidates scientific rationale behind each treatment atopic dermatitis.

Language: Английский

Citations

13
Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs DOI Creative Commons

Francoise Congues,

Pengcheng Wang, Joshua K. Lee

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 223, P. 116156 - 116156

Published: March 20, 2024

The skin, lung, and gut are important barrier organs that control how the body reacts to environmental stressors such as ultraviolet (UV) radiation, air pollutants, dietary components, microorganisms. aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor plays an role in maintaining homeostasis of organs. AhR was initially discovered for chemical carcinogens polycyclic aromatic hydrocarbons (PAHs). Activation pathways by PAHs leads increased DNA damage mutations which ultimately lead carcinogenesis. Ongoing evidence reveals ever-expanding AhR. Recently, has been linked immune systems interaction with development natural killer (NK) cells, regulatory T (T

Language: Английский

Citations

11
Inflammatory Skin Diseases: Focus on the Role of Suppressors of Cytokine Signaling (SOCS) Proteins DOI Creative Commons
Antonia Cianciulli, Rosa Calvello, Chiara Porro

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 505 - 505

Published: March 13, 2024

Inflammatory skin diseases include a series of disorders characterized by strong activation the innate and adaptive immune system in which proinflammatory cytokines play fundamental role supporting inflammation. Skin inflammation is complex process influenced various factors, including genetic environmental dysfunction both non-immune cells. Psoriasis (PS) atopic dermatitis (AD) are most common chronic inflammatory conditions whose pathogeneses very multifactorial. Both an immunological involving predominance Th1 Th17 cells PS Th2 AD. Suppressor cytokine signaling (SOCS) proteins intracellular that control responses regulating pathways activated cytokines. SOCS involved regulation progression skin-resident non-resident cells, recent data suggest these negative modulators dysregulated such as This review focuses on current understanding about modulating activity mediators implicated pathogenesis

Language: Английский

Citations

10
Innate Immune Sensing of AAV Vectors DOI

Di Cao,

Barry J. Byrne,

Ype P. de Jong

et al.

Human Gene Therapy, Journal Year: 2024, Volume and Issue: 35(13-14), P. 451 - 463

Published: June 18, 2024

Adeno-associated virus (AAV) based viral vectors are widely used in human gene therapy and form the basis of approved treatments for several genetic diseases. Immune responses to vector transgene products, however, substantially complicate these applications clinical practice. The role innate immune recognition AAV was initially unclear, given that inflammatory early after administration were typically mild animal models. However, more recent research continues identify pathways triggered by serve provide activation signals antigen-presenting cells initiation adaptive responses. Sensing genome endosomal DNA receptor toll-like 9 (TLR9) promotes response interferon expression. Thus, TLR9>MyD88 pathway plasmacytoid dendritic (pDCs) leads conditioning antigen cross-presenting DCs through type I (IFN-I) ultimately CD8

Language: Английский

Citations

10
Innate Immunity and Asthma Exacerbations: Insights From Human Models DOI
Jehan Alladina, Benjamin D. Medoff, Christina Schofield

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: March 1, 2025

ABSTRACT Asthma is a common chronic respiratory disease characterized by the presence of airway inflammation, hyperresponsiveness, and mucus hypersecretion. Repeated asthma exacerbations can lead to progressive remodeling irreversible airflow obstruction. Thus, understanding preventing are paramount importance. Although multiple endotypes exist, most often driven type 2 inflammation. New therapies that target specific mediators have been shown reduce frequency but incompletely effective in significant number asthmatics. Furthermore, it remains unknown whether current treatments sustained changes or if targeting additional pathways may be necessary achieve remission. Activation innate immunity initial event inflammatory sequence occurs during an exacerbation. However, there continue critical gaps our immune response exacerbating factors. In this review, we summarize role methods used study them. We also identify potential novel therapeutic targets for future areas investigation.

Language: Английский

Citations

1
Dietary Intake and Systemic Inflammation: Can We Use Food as Medicine? DOI
Erica Graff, Shyam Vedantam,

Mary Parianos

et al.

Current Nutrition Reports, Journal Year: 2023, Volume and Issue: 12(2), P. 247 - 254

Published: Jan. 20, 2023

Language: Английский

Citations

22
Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers DOI Creative Commons
C. Vanesa Díaz-García, Elena Moreno, Alba Talavera-Rodríguez

et al.

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 22, 2024

Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo. This double-masked, placebo-controlled pilot study assessed impacts of weekly placebo treatment over 8 weeks on 29 PWH receiving stable therapy (ART). Three stool donors high Faecalibacterium butyrate profiles were selected, their individual stools used for capsule preparation. Proteomic 345 proteins plasma quantified using proximity extension assay, samples collected at baseline 1, 8, 24. Concurrently, we characterized shifts composition annotated functions shotgun metagenomics. fitted generalized additive models dynamics protein expression. selected most relevant explore correlations functionality time linear mixed models. significantly reduced levels 45 proteins, including established mortality predictors such as IL6 TNF-α. found notable reductions persisting up 16 after final procedure, expression CCL20 CD22. identified 46 decreases FT3LG, IL6, IL10RB, IL12B, IL17A, which correlated multiple bacterial species. that specific species within Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, Clostridium genus, addition associated genes functions, markers. Targeting effectively decreased PWH, sustained effects. These findings suggest potential target mitigate inflammation-related complications this population, encouraging further research development microbiome-based interventions.

Language: Английский

Citations

7