AI Article Synopsis
- IL-25 is a Th2-related cytokine that reduces inflammation in colitis by promoting alternatively activated macrophages (AAMs), but the mechanism of this effect was previously unclear.
- The study revealed that IL-25 enhances AAM-related markers in macrophages and transfers AAMs from IL-25-treated mice reduced colitis severity in TNBS-induced colitis models.
- Although IL-25 increases cytokines like IL-4, IL-13, and TGF-β1 that promote AAM differentiation, blocking these cytokines did not stop IL-25's effect on AAM expression, confirming that IL-25's anticolitic role involves AAM induction.
Article Abstract
Background: Interleukin (IL)-25, a Th2-related factor, inhibits the synthesis of inflammatory cytokines by macrophages and attenuates experimental colitis in mice. The mechanism underlying the counterregulatory effect of IL-25, however, remains unknown. Since Th2-cytokines can abrogate inflammatory pathways by inducing alternatively activated macrophages (AAMs), we evaluated whether AAMs are involved in the IL-25-mediated anticolitic effect.
Methods: AAM-related markers were evaluated in peritoneal and lamina propria mononuclear cells of mice with or without 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis treated with IL-25 and/or neutralizing IL-4, IL-13, and transforming growth factor beta 1 (TGF-β1) antibodies. Peritoneal AAMs induced in vivo by injecting mice with IL-25 were transferred to mice with TNBS colitis. Finally, we assessed the in vitro effect of IL-25 on the alternative activation of peritoneal F4/80+ cells.
Results: IL-25 enhanced the expression of AAM-related markers in F4/80(+) cells infiltrating the peritoneum and colon of naïve and colitic mice. Peritoneal F4/80(+) cells isolated from IL-25-treated mice reduced the severity of TNBS colitis when injected intraperitoneally to recipient mice. Since IL-25 did not directly induce AAM in vitro and in vivo in mice, IL-25 administration enhanced the expression of IL-4, IL-13, and TGF-β1, which are known to promote AAM differentiation, we finally assessed whether such cytokines were involved in the IL-25-driven AAM induction. Blockade of IL-4, IL-13, and TGF-β1 with neutralizing antibodies in mice did not inhibit the stimulatory effect of IL-25 on AAM gene expression.
Conclusions: The IL-25-mediated anticolitic effect is associated with induction of AAMs, a subset of macrophages with antiinflammatory properties.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ibd.21799 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Activation of PPARγ regulates M1/M2 macrophage polarization and attenuates dextran sulfate sodium salt-induced inflammatory bowel disease via the STAT-1/STAT-6 pathway.
Kaohsiung J Med Sci
December 2024
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
This study aimed to investigate whether activation of PPARγ regulates M1/M2 macrophage polarization to attenuate dextran sulfate sodium salt (DSS)-induced inflammatory bowel disease (IBD) via the STAT-1/STAT-6 pathway in vivo and in vitro. We first examined the effect of PPARγ on macrophage polarization in LPS/IFN-γ-treated M1 RAW264.7 cells and IL-4/IL-13-treated M2 RAW264.
View Article and Find Full Text PDFBLOC1S1 Control of Vacuolar Organelle Fidelity Modulates Murine T2 Cell Immunity and Allergy Susceptibility.
Allergy
December 2024
Laboratory of Mitochondrial Biology and Metabolism, NHLBI, NIH, Bethesda, Maryland, USA.
Background: The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4 T cells may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity.
View Article and Find Full Text PDFAnti-IL-4Ra therapy is superior to other biologic classes in treating allergic bronchopulmonary aspergillosis.
J Allergy Clin Immunol Glob
February 2025
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to . Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.
Objective: We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.
Updates on the Pathogenesis of Canine Atopic Dermatitis and Feline Atopic Skin Syndrome: Part 2, the Skin Barrier, the Microbiome, and Immune System Dysfunction.
Vet Clin North Am Small Anim Pract
December 2024
College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 408 Raymond Stotzer Parkway, College Station, TX 77845, USA. Electronic address:
Alterations in the lipid layer and intercellular corneocyte connections can lead to increased allergen penetration through the skin surface. A normal cutaneous microbiome keeps the opportunistic pathogen Staphylococcus pseudintermedius levels low, but allergic inflammation leads to decreased diversity and increase in S pseudintermedius. Keratinocytes sound the initial allergen alarm via cytokine signaling and promote T-helper 2 (Th-2) inflammation.
View Article and Find Full Text PDFCharacterization of Serum Cytokine Patterns in Frequent-Exacerbation Asthma: Implications for Phenotyping and Management.
Adv Respir Med
December 2024
Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi 12100, Vietnam.
(1) Background: Asthma exacerbations represent significant clinical events, however, the underlying inflammatory mechanisms and cytokine profiles in patients with frequent exacerbations remain incompletely understood; (2) Methods: In this prospective, cross-sectional study of 120 stable asthma patients, we compared the serum concentrations of eight key cytokines (IL-4, IL-12, IL-13, IL-17, IFN-α, IFN-γ, TNF-α, and IL-1β) between two groups: 60 patients with frequent exacerbations (≥ 2 events per year) and 60 matched controls with few exacerbations (1 event per year); (3) Results: Patients with frequent exacerbations showed significantly higher serum concentrations of IL-4 and IL-13 ( < 0.05), along with an increased prevalence of allergic history and comorbidities (chronic rhinosinusitis, GERD, OSA; all < 0.05).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!