Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life

IntroductionAsthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.MethodsWe clinically examined the influence of vitamin D...

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Main Authors: Yan Zhou, Yali Qiu, Wuping Bao, Lei Han, Yishu Xue, Yingying Zhang, Xue Tian, Qiang Fu, Chengjian Lv, Dongning Yin, Min Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107031/full
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author Yan Zhou
Yali Qiu
Wuping Bao
Lei Han
Yishu Xue
Yingying Zhang
Xue Tian
Qiang Fu
Chengjian Lv
Dongning Yin
Min Zhang
author_facet Yan Zhou
Yali Qiu
Wuping Bao
Lei Han
Yishu Xue
Yingying Zhang
Xue Tian
Qiang Fu
Chengjian Lv
Dongning Yin
Min Zhang
author_sort Yan Zhou
collection DOAJ
description IntroductionAsthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.MethodsWe clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish “T2-high” asthma or OVA combined with ozone exposure (OVA + ozone) to induce “T2-low” asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed.ResultsSerum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma.DiscussionThe potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.
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spelling doaj.art-73f25454d4c3446bb7fc059e8120afea2023-01-30T03:46:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.11070311107031Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-lifeYan Zhou0Yali Qiu1Wuping Bao2Lei Han3Yishu Xue4Yingying Zhang5Xue Tian6Qiang Fu7Chengjian Lv8Dongning Yin9Min Zhang10Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, ChinaIntroductionAsthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.MethodsWe clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish “T2-high” asthma or OVA combined with ozone exposure (OVA + ozone) to induce “T2-low” asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed.ResultsSerum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma.DiscussionThe potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107031/fullvitamin Dairway inflammationairway resistanceasthma endotypesT2-low asthma
spellingShingle Yan Zhou
Yali Qiu
Wuping Bao
Lei Han
Yishu Xue
Yingying Zhang
Xue Tian
Qiang Fu
Chengjian Lv
Dongning Yin
Min Zhang
Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
Frontiers in Immunology
vitamin D
airway inflammation
airway resistance
asthma endotypes
T2-low asthma
title Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
title_full Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
title_fullStr Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
title_full_unstemmed Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
title_short Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life
title_sort evaluating the effects of vitamin d level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin d during early life
topic vitamin D
airway inflammation
airway resistance
asthma endotypes
T2-low asthma
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107031/full
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