scholarly journals Streptococcus pneumoniae aminopeptidase N regulates dendritic cells that attenuates type‐2 airway inflammation in murine allergic asthma

2020 ◽  
Vol 177 (22) ◽  
pp. 5063-5077
Author(s):  
Guangying Wu ◽  
Xuemei Zhang ◽  
Xu Chen ◽  
Jian Wang ◽  
Jing Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Streptococcus Pneumoniae ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Aminopeptidase N

scholarly journals Dendritic Cells: Critical Regulators of Allergic Asthma

2020 ◽  
Vol 21 (21) ◽  
pp. 7930 ◽  
Author(s):  
Ioannis Morianos ◽  
Maria Semitekolou
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Allergic Airway Inflammation ◽  
Chronic Inflammatory Disease ◽  
Antigen Presenting ◽  
Airborne Allergens

Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), chronic airway inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system that act as a bridge between innate and adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known to play a central role in initiating and maintaining allergen driven Th2 immune responses in the airways. Nevertheless, seminal studies have demonstrated that DCs can also restrain excessive asthmatic responses and thus contribute to the resolution of allergic airway inflammation and the maintenance of pulmonary tolerance. Notably, the transfer of tolerogenic DCs in vivo suppresses Th2 allergic responses and protects or even reverses established allergic airway inflammation. Thus, the identification of novel DC subsets that possess immunoregulatory properties and can efficiently control aberrant asthmatic responses is critical for the re-establishment of tolerance and the amelioration of the asthmatic disease phenotype.

scholarly journals Irg1/itaconate metabolic pathway is a crucial determinant of dendritic cells immune-priming function and contributes to resolute allergen-induced airway inflammation

2021 ◽  
Author(s):  
Anil Kumar Jaiswal ◽  
Jyoti Yadav ◽  
Sangeet Makhija ◽  
Suman Mazumder ◽  
Amit Kumar Mitra ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Allergic Sensitization ◽  
Mucous Cell ◽  
Th2 Immune Response ◽  
Pulsed Dc

AbstractItaconate is produced from the mitochondrial TCA cycle enzyme aconitase decarboxylase (encoded by immune responsive gene1; Irg1) that exerts immunomodulatory function in myeloid cells. However, the role of the Irg1/itaconate pathway in dendritic cells (DC)-mediated airway inflammation and adaptive immunity to inhaled allergens, which are the primary antigen-presenting cells in allergic asthma, remains largely unknown. House dust mite (HDM)-challenged Irg1−/− mice displayed increases in eosinophilic airway inflammation, mucous cell metaplasia, and Th2 cytokine production with a mechanism involving impaired mite antigen presentations by DC. Adoptive transfer of HDM-pulsed DC from Irg1-deficient mice into naïve WT mice induced a similar phenotype of elevated type 2 airway inflammation and allergic sensitization. Untargeted metabolite analysis of HDM-pulsed DC revealed itaconate as one of the most abundant polar metabolites that potentially suppress mitochondrial oxidative damage. Furthermore, the immunomodulatory effect of itaconate was translated in vivo, where intranasal administration of 4-octyl itaconate 4-OI following antigen priming attenuated the manifestations of HDM-induced airway disease and Th2 immune response. Taken together, these data demonstrated for the first time a direct regulatory role of the Irg1/itaconate pathway in DC for the development of type 2 airway inflammation and suggest a possible therapeutic target in modulating allergic asthma.

scholarly journals Inhaled house dust programs pulmonary dendritic cells to promote type 2 T-cell responses by an indirect mechanism

2015 ◽  
Vol 309 (10) ◽  
pp. L1208-L1218 ◽  
Author(s):  
Timothy P. Moran ◽  
Keiko Nakano ◽  
Gregory S. Whitehead ◽  
Seddon Y. Thomas ◽  
Donald N. Cook ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Allergic Asthma ◽  
House Dust ◽  
Lavage Fluid ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Cell Responses ◽  
Th2 Responses ◽  
Th2 Differentiation

The induction of allergen-specific T helper 2 (Th2) cells by lung dendritic cells (DCs) is a critical step in allergic asthma development. Airway delivery of purified allergens or microbial products can promote Th2 priming by lung DCs, but how environmentally relevant quantities and combinations of these factors affect lung DC function is unclear. Here, we investigated the ability of house dust extract (HDE), which contains a mixture of environmental adjuvants, to prime Th2 responses against an innocuous inhaled antigen. Inhalational exposure to HDE conditioned lung conventional DCs, but not monocyte-derived DCs, to induce antigen-specific Th2 differentiation. Conditioning of DCs by HDE was independent of Toll-like receptor 4 signaling, indicating that environmental endotoxin is dispensable for programming DCs to induce Th2 responses. DCs directly treated with HDE underwent maturation but were poor stimulators of Th2 differentiation. In contrast, DCs treated with bronchoalveolar lavage fluid (BALF) from HDE-exposed mice induced robust Th2 differentiation. DC conditioning by BALF was independent of the proallergic cytokines IL-25, IL-33, and thymic stromal lymphopoietin. BALF treatment of DCs resulted in upregulation of CD80 but low expression of CD40, CD86, and IL-12p40, which was associated with Th2 induction. These findings support a model whereby environmental adjuvants in house dust indirectly program DCs to prime Th2 responses by triggering the release of endogenous soluble factor(s) by airway cells. Identifying these factors could lead to novel therapeutic targets for allergic asthma.

scholarly journals Neonatal Streptococcus pneumoniae Pneumonia Induces an Aberrant Airway Smooth Muscle Phenotype and AHR in Mice Model

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xin Peng ◽  
Yi Wu ◽  
Xiao Kong ◽  
Yunxiu Chen ◽  
Yonglu Tian ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Streptococcus Pneumoniae ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cells ◽  
Pivotal Role ◽  
Mice Model ◽  
Asthma Model

Our previous study showed that neonatal S. pneumoniae infection aggravated airway inflammation and airway hyperresponsiveness (AHR) in an OVA-induced allergic asthma model. As airway smooth muscle (ASM) plays a pivotal role in AHR development, we aim to investigate the effects of neonatal S. pneumoniae pneumonia on ASM structure and AHR development. Non-lethal neonatal pneumonia was established by intranasally infecting 1-week-old BALB/C mice with the S. pneumoniae strain D39. Five weeks after infection, the lungs were collected to assess the levels of α-SMA and the contractile proteins of ASM. Our results indicate that neonatal S. pneumoniae pneumonia significantly increased adulthood lung α-SMA and SMMHC proteins production and aggravated airway inflammatory cells infiltration and cytokines release. In addition, the neonatal S. pneumoniae pneumonia group had significantly higher Penh values compared to the uninfected controls. These data suggest that neonatal S. pneumoniae pneumonia promoted an aberrant ASM phenotype and AHR development in mice model.

scholarly journals Jagged1-expressing adenovirus-infected dendritic cells induce expansion of Foxp3+ regulatory T cells and alleviate T helper type 2-mediated allergic asthma in mice

Immunology ◽  
2018 ◽  
Vol 156 (2) ◽  
pp. 199-212 ◽  
Author(s):  
Chu-Lun Lin ◽  
Huei-Mei Huang ◽  
Chia-Ling Hsieh ◽  
Chia-Kwung Fan ◽  
Yueh-Lun Lee
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Allergic Asthma ◽  
T Helper ◽  
Helper Type

scholarly journals Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms

2019 ◽  
Vol 12 (597) ◽  
pp. eaax3332 ◽  
Author(s):  
Brenal K. Singh ◽  
Wen Lu ◽  
Amanda M. Schmidt Paustian ◽  
Moyar Q. Ge ◽  
Cynthia J. Koziol-White ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
Airway Disease ◽  
Negative Regulator ◽  
Airway Smooth Muscle Cells ◽  
T Helper 2

Asthma is a chronic allergic inflammatory airway disease caused by aberrant immune responses to inhaled allergens, which leads to airway hyperresponsiveness (AHR) to contractile stimuli and airway obstruction. Blocking T helper 2 (TH2) differentiation represents a viable therapeutic strategy for allergic asthma, and strong TCR-mediated ERK activation blocks TH2 differentiation. Here, we report that targeting diacylglycerol (DAG) kinase zeta (DGKζ), a negative regulator of DAG-mediated cell signaling, protected against allergic asthma by simultaneously reducing airway inflammation and AHR though independent mechanisms. Targeted deletion of DGKζ in T cells decreased type 2 inflammation without reducing AHR. In contrast, loss of DGKζ in airway smooth muscle cells decreased AHR but not airway inflammation. T cell–specific enhancement of ERK signaling was only sufficient to limit type 2 airway inflammation, not AHR. Pharmacological inhibition of DGK diminished both airway inflammation and AHR in mice and also reduced bronchoconstriction of human airway samples in vitro. These data suggest that DGK is a previously unrecognized therapeutic target for asthma and reveal that the inflammatory and AHR components of asthma are not as interdependent as generally believed.

scholarly journals Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice

2020 ◽  
Vol 21 (24) ◽  
pp. 9508
Author(s):  
Sang Chul Park ◽  
Dahee Shim ◽  
Hongmin Kim ◽  
Yeeun Bak ◽  
Da Yeon Choi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Tyrosine Kinase ◽  
Allergic Asthma ◽  
Lung Inflammation ◽  
In Vivo Models ◽  
Allergic Lung Inflammation ◽  
Th2 Responses

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103+ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b+ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.

Myeloid dendritic cells type 2 in allergic asthma

Allergy ◽  
2013 ◽  
Vol 68 (10) ◽  
pp. 1322-1326 ◽  
Author(s):  
B. Dua ◽  
S. Smith ◽  
T. Kinoshita ◽  
H. Imaoka ◽  
G. Gauvreau ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Allergic Asthma ◽  
Myeloid Dendritic Cells
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