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Immunoregulatory Role of HLA-G in Allergic Diseases.

ABSTRACT: Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

SUBMITTER: Murdaca G

PROVIDER: S-EPMC4931064 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Immunoregulatory Role of HLA-G in Allergic Diseases.

Murdaca Giuseppe G Contini Paola P Negrini Simone S Ciprandi Giorgio G Puppo Francesco F

Journal of immunology research 20160620

Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G) molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug ...[more]

PMID: 27413762

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Project description:BackgroundNicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development.ObjectiveWe examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.MethodsIn the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.ResultsTryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.Conclusions and clinical relevanceMaternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

Project description:The prevalence and incidence of allergic diseases is rising and these diseases have become the most common chronic diseases during childhood in Westernized countries. Early life forms a critical window predisposing for health or disease. Therefore, this can also be a window of opportunity for allergy prevention. Postnatally the gut needs to mature, and the microbiome is built which further drives the training of infant's immune system. Immunomodulatory components in breastmilk protect the infant in this crucial period by; providing nutrients that contain substrates for the microbiome, supporting intestinal barrier function, protecting against pathogenic infections, enhancing immune development and facilitating immune tolerance. The presence of a diverse human milk oligosaccharide (HMOS) mixture, containing several types of functional groups, points to engagement in several mechanisms related to immune and microbiome maturation in the infant's gastrointestinal tract. In recent years, several pathways impacted by HMOS have been elucidated, including their capacity to; fortify the microbiome composition, enhance production of short chain fatty acids, bind directly to pathogens and interact directly with the intestinal epithelium and immune cells. The exact mechanisms underlying the immune protective effects have not been fully elucidated yet. We hypothesize that HMOS may be involved in and can be utilized to provide protection from developing allergic diseases at a young age. In this review, we highlight several pathways involved in the immunomodulatory effects of HMOS and the potential role in prevention of allergic diseases. Recent studies have proposed possible mechanisms through which HMOS may contribute, either directly or indirectly, via microbiome modification, to induce oral tolerance. Future research should focus on the identification of specific pathways by which individual HMOS structures exert protective actions and thereby contribute to the capacity of the authentic HMOS mixture in early life allergy prevention.

Project description:(1) Background: The atopic march is defined by the increased prevalence of allergic diseases after atopic dermatitis onset. In fact, atopic dermatitis is believed to play an important role in allergen sensitization via the damaged skin barrier, leading to allergic diseases such as allergic asthma and allergic rhinitis. The eosinophil, a pro-inflammatory cell that contributes to epithelial damage, is one of the various cells recruited in the inflammatory reactions characterizing these diseases. Few studies were conducted on the transcriptome of this cell type and even less on their specific microRNA (miRNA) profile, which could modulate pathogenesis of allergic diseases and clinical manifestations post-transcriptionally. Actually, their implication in allergic diseases is not fully understood, but they are believed to play a role in inflammation-related patterns and epithelial cell proliferation. (2) Methods: Next-generation sequencing was performed on RNA samples from eosinophils of individuals with atopic dermatitis, atopy, allergic rhinitis and asthma to obtain differential counts of primary miRNA (pri-miRNA); these were also analyzed for asthma-related phenotypes such as forced expiratory volume in one second (FEV1), immunoglobulin E (IgE) and provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 s (PC20) levels, as well as FEV1 to forced vital capacity (FEV1/FVC) ratio. (3) Results: Eighteen miRNAs from eosinophils were identified to be significantly different between affected individuals and unaffected ones. Based on counts from these miRNAs, individuals were then clustered into groups using Ward's method on Euclidian distances. Groups were found to be explained by asthma diagnosis, familial history of respiratory diseases and allergic rhinitis as well as neutrophil counts. (4) Conclusions: The 18 differential miRNA counts for the studying phenotypes allow a better understanding of the epigenetic mechanisms underlying the development of the allergic diseases included in the atopic march.

Dataset Information

Immunoregulatory Role of HLA-G in Allergic Diseases.

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Immunoregulatory Role of HLA-G in Allergic Diseases.

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