T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB(+) CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB(-) CRS. Ssps were detected in the stool protein extracts from FA patients with SEB(+) CRS, but not in those with SEB(-) CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4(+) T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB(+) CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.
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http://dx.doi.org/10.1038/cmi.2012.32 | DOI Listing |
Expert Rev Respir Med
January 2025
School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
Introduction: In genetically predisposed individuals, exposure to aeroallergens and infections from RNA viruses shape epithelial barrier function, leading to Allergic Asthma (AA). Here, activated pattern recognition receptors (PRRs) in lower airway sentinel cells signal epithelial injury-repair pathways leading to cell-state changes [epithelial mesenchymal plasticity (EMP)], barrier disruption and sensitization.
Areas Covered: 1.
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 PDFBiochim Biophys Acta Mol Basis Dis
December 2024
State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy & Immunology of Shenzhen University School of Medicine, Shenzhen, China. Electronic address:
The pathogenesis of many immune disorders is linked to regulatory macrophage dysfunction. The mechanism underlying it is unclear. The objective of this study is to examine the mechanism by which the PRKN ubiquitin protein ligase (PRKN) inhibits the development of regulatory macrophages (Mreg).
View Article and Find Full Text PDFCell Commun Signal
December 2024
Department of Otolaryngology of Longgang Central Hospital and Clinical College Affiliated to Guangzhou University of Chinese Medicine, Shenzhen, China.
Background: It is well-known that Dendritic cells (DCs) are essential in the development of airway Th2 polarization and airway allergy (AA). The underlying mechanism is still not fully understood. The objective of this study is to examine the role of methyltransferase-like protein-5 (Mettl5), a methyltransferase involved in N6-methyladenosine (m6A) methylation, in altering DC's properties to facilitate the development of Th2 polarization and AA.
View Article and Find Full Text PDFFront Immunol
December 2024
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
The Natural Killer T cells (NKT) are a unique subset of T lymphocytes that recognize lipid-based antigens that are presented by the monomorphic MHC-I-like molecule, CD1d. Over 30 years ago, the discovery of the glycolipid α-Galactosylceramide (α-GalCer) from the marine sponge , as a potent activator of the invariant Natural Killer T (iNKT) cells, has attracted great attention for its use in cancer immunotherapy. However, α-GalCer can initiate both pro-inflammatory T helper cell 1 (Th1) and anti-inflammatory Th2 type immune responses that can result in either enhanced or suppressed immunity in a somewhat unpredictable manner.
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