Pub Date : 2024-02-07DOI: 10.3389/falgy.2024.1307880
S. Fernandez-Bravo, Diana Betancor, Javier Cuesta-Herranz, Pablo Rodríguez del Río, M. Ibáñez-Sandín, E. Nuñez-Borque, Vanesa Esteban
Anaphylaxis is the most severe manifestation of allergic disorders. Currently, an increasing number of cells, pathways and molecules involved in the etiopathogenesis of anaphylaxis are being discovered. However, there are no conclusive biomarkers to confirm its diagnosis. Small non-coding RNAs (sncRNAs) are 18-200 nucleotide molecules that can be divided into: microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transference RNA derived fragments (tRFs) and YRNA derived fragments (YRFs). These molecules participate in cell-cell communication modulating various physiological processes and have been postulated as non-invasive biomarkers of several pathologies. Therefore, in this study we characterized the serum circulating profile of other sncRNA beyond miRNAs in two populations of 5 adults and 5 children with drug- and food-mediated anaphylaxis, respectively.Samples were obtained from each patient under two different conditions: during anaphylaxis and 14 days after the reaction (control). The sncRNA analysis was carried out by Next Generation Sequencing (NGS).A total of 671 sncRNAs (3 piRNAs, 74 snoRNAs, 54 snRNAs, 348 tRFs and 192 YRFs) were identified in adults with drug-induced anaphylaxis, while 612 sncRNAs (2 piRNAs, 73 snoRNAs, 52 snRNAs, 321 tRFs and 164 YRFs) were characterized in children with food-mediated anaphylaxis. However, only 33 (1 piRNA, 4 snoRNAs, 1 snRNAs, 7 tRFs and 20 YRFs) and 80 (4 snoRNAs, 6 snRNAs, 54 tRFs and 16 YRFs) of them were statistically different between both conditions, respectively. Among them, only three (Y_RNA.394, Y_RNA.781 and SCARNA2) were common to both adults and children analysis.This study provides a differential profile of circulating serum sncRNAs beyond miRNAs in patients with anaphylaxis, postulating them as candidate biomarkers for this pathological event and as novel mediators of the reaction.
{"title":"Circulating serum profile of small non-coding RNAs in patients with anaphylaxis beyond microRNAs","authors":"S. Fernandez-Bravo, Diana Betancor, Javier Cuesta-Herranz, Pablo Rodríguez del Río, M. Ibáñez-Sandín, E. Nuñez-Borque, Vanesa Esteban","doi":"10.3389/falgy.2024.1307880","DOIUrl":"https://doi.org/10.3389/falgy.2024.1307880","url":null,"abstract":"Anaphylaxis is the most severe manifestation of allergic disorders. Currently, an increasing number of cells, pathways and molecules involved in the etiopathogenesis of anaphylaxis are being discovered. However, there are no conclusive biomarkers to confirm its diagnosis. Small non-coding RNAs (sncRNAs) are 18-200 nucleotide molecules that can be divided into: microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transference RNA derived fragments (tRFs) and YRNA derived fragments (YRFs). These molecules participate in cell-cell communication modulating various physiological processes and have been postulated as non-invasive biomarkers of several pathologies. Therefore, in this study we characterized the serum circulating profile of other sncRNA beyond miRNAs in two populations of 5 adults and 5 children with drug- and food-mediated anaphylaxis, respectively.Samples were obtained from each patient under two different conditions: during anaphylaxis and 14 days after the reaction (control). The sncRNA analysis was carried out by Next Generation Sequencing (NGS).A total of 671 sncRNAs (3 piRNAs, 74 snoRNAs, 54 snRNAs, 348 tRFs and 192 YRFs) were identified in adults with drug-induced anaphylaxis, while 612 sncRNAs (2 piRNAs, 73 snoRNAs, 52 snRNAs, 321 tRFs and 164 YRFs) were characterized in children with food-mediated anaphylaxis. However, only 33 (1 piRNA, 4 snoRNAs, 1 snRNAs, 7 tRFs and 20 YRFs) and 80 (4 snoRNAs, 6 snRNAs, 54 tRFs and 16 YRFs) of them were statistically different between both conditions, respectively. Among them, only three (Y_RNA.394, Y_RNA.781 and SCARNA2) were common to both adults and children analysis.This study provides a differential profile of circulating serum sncRNAs beyond miRNAs in patients with anaphylaxis, postulating them as candidate biomarkers for this pathological event and as novel mediators of the reaction.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139795347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-07DOI: 10.3389/falgy.2024.1330517
M. Félix, F. Kuschnir, J. Boechat, Mariana Castells
Drug hypersensitivity reactions (DHR) in children have a significant impact on clinical practice and public health. Both under-diagnosis (due to under-reporting) and over-diagnosis (due to the overuse of the term “allergy”) are potential issues. The aim of this narrative review is to describe the most recent findings of DHR in children/adolescents and gaps regarding epidemiology, antibiotic allergy, antiepileptic hypersensitivity, vaccine allergy, and severe cutaneous adverse reactions (SCAR) in this age group.
{"title":"Recent findings on drug hypersensitivity in children","authors":"M. Félix, F. Kuschnir, J. Boechat, Mariana Castells","doi":"10.3389/falgy.2024.1330517","DOIUrl":"https://doi.org/10.3389/falgy.2024.1330517","url":null,"abstract":"Drug hypersensitivity reactions (DHR) in children have a significant impact on clinical practice and public health. Both under-diagnosis (due to under-reporting) and over-diagnosis (due to the overuse of the term “allergy”) are potential issues. The aim of this narrative review is to describe the most recent findings of DHR in children/adolescents and gaps regarding epidemiology, antibiotic allergy, antiepileptic hypersensitivity, vaccine allergy, and severe cutaneous adverse reactions (SCAR) in this age group.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139858057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.3389/falgy.2024.1298816
Antonio Nieto-García, Eva Abel-Fernández, María Nieto-Cid, Fernando Pineda de la Losa
In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.
近年来，利用分子技术诊断过敏症取得了一些重要进展。利用过敏原的分子成分对过敏进行病原学诊断，可以更精确地确定患者的 IgE 基因库。精准医学是一种结构模式，旨在实现个性化医疗保健，并将患者置于专家决策过程的中心。为此，在分子水平上准确描述外部暴露体的特征及其作为临床相关过敏原的作用，对于阐明特应性疾病的表型多样性至关重要，从而实现个性化诊断和治疗。有人提出了一种决策算法，即 "自上而下 "法，首先确定临床病史，然后使用皮肤测试或特异性 IgE 技术，这有助于临床医生做出决策。由标准诊断方法驱动的治疗干预，在这些创新工具的支持下，可以更好地对高度复杂的患者进行表型分析，并开出更合适的 AIT 处方。为此，用于诊断的过敏原提取物必须质量可靠，并含有最相关的过敏原。同样，过敏原疫苗也必须具备有效性、安全性、持续时间和患者依从性，因此需要新疫苗来克服这些缺点。
{"title":"360° approach to the patient with mite allergy: from scientific evidence to clinical practice","authors":"Antonio Nieto-García, Eva Abel-Fernández, María Nieto-Cid, Fernando Pineda de la Losa","doi":"10.3389/falgy.2024.1298816","DOIUrl":"https://doi.org/10.3389/falgy.2024.1298816","url":null,"abstract":"In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139799216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.3389/falgy.2024.1298816
Antonio Nieto-García, Eva Abel-Fernández, María Nieto-Cid, Fernando Pineda de la Losa
In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.
近年来，利用分子技术诊断过敏症取得了一些重要进展。利用过敏原的分子成分对过敏进行病原学诊断，可以更精确地确定患者的 IgE 基因库。精准医学是一种结构模式，旨在实现个性化医疗保健，并将患者置于专家决策过程的中心。为此，在分子水平上准确描述外部暴露体的特征及其作为临床相关过敏原的作用，对于阐明特应性疾病的表型多样性至关重要，从而实现个性化诊断和治疗。有人提出了一种决策算法，即 "自上而下 "法，首先确定临床病史，然后使用皮肤测试或特异性 IgE 技术，这有助于临床医生做出决策。由标准诊断方法驱动的治疗干预，在这些创新工具的支持下，可以更好地对高度复杂的患者进行表型分析，并开出更合适的 AIT 处方。为此，用于诊断的过敏原提取物必须质量可靠，并含有最相关的过敏原。同样，过敏原疫苗也必须具备有效性、安全性、持续时间和患者依从性，因此需要新疫苗来克服这些缺点。
{"title":"360° approach to the patient with mite allergy: from scientific evidence to clinical practice","authors":"Antonio Nieto-García, Eva Abel-Fernández, María Nieto-Cid, Fernando Pineda de la Losa","doi":"10.3389/falgy.2024.1298816","DOIUrl":"https://doi.org/10.3389/falgy.2024.1298816","url":null,"abstract":"In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139858823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-05DOI: 10.3389/falgy.2024.1368259
Luis Garcia-Marcos
{"title":"Grand challenges in genetics and epidemiology of allergic diseases: from genome to exposome and back","authors":"Luis Garcia-Marcos","doi":"10.3389/falgy.2024.1368259","DOIUrl":"https://doi.org/10.3389/falgy.2024.1368259","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139863567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-05DOI: 10.3389/falgy.2024.1368259
Luis Garcia-Marcos
{"title":"Grand challenges in genetics and epidemiology of allergic diseases: from genome to exposome and back","authors":"Luis Garcia-Marcos","doi":"10.3389/falgy.2024.1368259","DOIUrl":"https://doi.org/10.3389/falgy.2024.1368259","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139803759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.3389/falgy.2024.1357886
Raquel López-Rodríguez, Irina Bobolea, Carlos Melero, M. Rial
{"title":"Editorial: A multidisciplinary approach to treatment of severe chronic airway disease (CAD): focus on biomarkers","authors":"Raquel López-Rodríguez, Irina Bobolea, Carlos Melero, M. Rial","doi":"10.3389/falgy.2024.1357886","DOIUrl":"https://doi.org/10.3389/falgy.2024.1357886","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139870581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.3389/falgy.2024.1357886
Raquel López-Rodríguez, Irina Bobolea, Carlos Melero, M. Rial
{"title":"Editorial: A multidisciplinary approach to treatment of severe chronic airway disease (CAD): focus on biomarkers","authors":"Raquel López-Rodríguez, Irina Bobolea, Carlos Melero, M. Rial","doi":"10.3389/falgy.2024.1357886","DOIUrl":"https://doi.org/10.3389/falgy.2024.1357886","url":null,"abstract":"","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139810816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-30eCollection Date: 2023-01-01DOI: 10.3389/falgy.2023.1291185
G K Scadding, M McDonald, V Backer, G Scadding, M Bernal-Sprekelsen, D M Conti, E De Corso, Z Diamant, C Gray, C Hopkins, M Jesenak, P Johansen, J Kappen, J Mullol, D Price, S Quirce, S Reitsma, S Salmi, B Senior, J P Thyssen, U Wahn, P W Hellings
Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.
{"title":"Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1-allergic asthma.","authors":"G K Scadding, M McDonald, V Backer, G Scadding, M Bernal-Sprekelsen, D M Conti, E De Corso, Z Diamant, C Gray, C Hopkins, M Jesenak, P Johansen, J Kappen, J Mullol, D Price, S Quirce, S Reitsma, S Salmi, B Senior, J P Thyssen, U Wahn, P W Hellings","doi":"10.3389/falgy.2023.1291185","DOIUrl":"10.3389/falgy.2023.1291185","url":null,"abstract":"<p><p>Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.</p>","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-26DOI: 10.3389/falgy.2024.1323405
S. Proper, Alexander T. Dwyer, Andrews Appiagyei, J. Felton, Netali Ben-Baruch Morgenstern, Justin M. Marlman, M. Kotliar, Artem Barski, Ty D. Troutman, Marc E. Rothenberg, T. Mersha, N. Azouz
Atopic dermatitis (AD) is an allergic skin disease mediated by skin barrier impairment and IL-13-driven immune response. Activation of the aryl hydrocarbon receptor (AHR) has shown promise in early clinical trials for AD; however, the mechanism by which AHR partially ameliorates AD is not well known.Gene expression data from human biopsies were analyzed, and compared to gene expression from RNA-sequencing in our in-vitro HaCaT cell model system. Western blot, ELISA qRT-PCR were used to further explore the relationship between AHR and IL-13 signaling in HaCaT cells.The AHR target gene CYP1A1 was decreased in lesional skin compared with healthy control skin (p = 4.30 × 10−9). Single-cell RNA sequencing (scRNAseq) demonstrated increased AHR expression (p < 1.0 × 10−4) and decreased CYP1A1 expression in lesional AD keratinocytes compared with healthy control keratinocytes (p < 0.001). Activation of AHR by AHR agonists in HaCaT cells reversed IL-13-dependent gene expression of several key genes in AD pathogenesis, most notably the eosinophil chemoattractant CCL26 (eotaxin-3). Differentially expressed genes in keratinocytes of patients with AD substantially overlapped with genes regulated by AHR agonists from HaCaT cells by RNAseq, but in reverse direction. Mechanistically, there was evidence for direct transcriptional effects of AHR; AHR binding motifs were identified in the differentially expressed genes from lesional AD keratinocytes compared to control keratinocytes, and AHR activation did not modify IL-13-dependent signal transducer and activator of transcription 6 (STAT6) translocation to the nucleus.Together, these data suggest that the AHR pathway is dysregulated in AD and that AHR modulates IL-13 downstream signaling in keratinocytes through genome-wide, transcriptional regulatory effects.
{"title":"Aryl hydrocarbon receptor and IL-13 signaling crosstalk in human keratinocytes and atopic dermatitis","authors":"S. Proper, Alexander T. Dwyer, Andrews Appiagyei, J. Felton, Netali Ben-Baruch Morgenstern, Justin M. Marlman, M. Kotliar, Artem Barski, Ty D. Troutman, Marc E. Rothenberg, T. Mersha, N. Azouz","doi":"10.3389/falgy.2024.1323405","DOIUrl":"https://doi.org/10.3389/falgy.2024.1323405","url":null,"abstract":"Atopic dermatitis (AD) is an allergic skin disease mediated by skin barrier impairment and IL-13-driven immune response. Activation of the aryl hydrocarbon receptor (AHR) has shown promise in early clinical trials for AD; however, the mechanism by which AHR partially ameliorates AD is not well known.Gene expression data from human biopsies were analyzed, and compared to gene expression from RNA-sequencing in our in-vitro HaCaT cell model system. Western blot, ELISA qRT-PCR were used to further explore the relationship between AHR and IL-13 signaling in HaCaT cells.The AHR target gene CYP1A1 was decreased in lesional skin compared with healthy control skin (p = 4.30 × 10−9). Single-cell RNA sequencing (scRNAseq) demonstrated increased AHR expression (p < 1.0 × 10−4) and decreased CYP1A1 expression in lesional AD keratinocytes compared with healthy control keratinocytes (p < 0.001). Activation of AHR by AHR agonists in HaCaT cells reversed IL-13-dependent gene expression of several key genes in AD pathogenesis, most notably the eosinophil chemoattractant CCL26 (eotaxin-3). Differentially expressed genes in keratinocytes of patients with AD substantially overlapped with genes regulated by AHR agonists from HaCaT cells by RNAseq, but in reverse direction. Mechanistically, there was evidence for direct transcriptional effects of AHR; AHR binding motifs were identified in the differentially expressed genes from lesional AD keratinocytes compared to control keratinocytes, and AHR activation did not modify IL-13-dependent signal transducer and activator of transcription 6 (STAT6) translocation to the nucleus.Together, these data suggest that the AHR pathway is dysregulated in AD and that AHR modulates IL-13 downstream signaling in keratinocytes through genome-wide, transcriptional regulatory effects.","PeriodicalId":73062,"journal":{"name":"Frontiers in allergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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