Targeting SIRP-α protects from type 2-driven allergic airway inflammation

2010 ◽  
Vol 40 (12) ◽  
pp. 3510-3518 ◽  
Author(s):  
Marianne Raymond ◽  
Vu Quang Van ◽  
Manuel Rubio ◽  
Karl Welzenbach ◽  
Marika Sarfati
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. airway hyperresponsiveness

2015 ◽  
Vol 309 (8) ◽  
pp. L789-L800 ◽  
Author(s):  
Akihiko Taniguchi ◽  
Nobuaki Miyahara ◽  
Koichi Waseda ◽  
Etsuko Kurimoto ◽  
Utako Fujii ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Group 2 ◽  
Airway Responses

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE−/− mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation

2021 ◽  
Author(s):  
Joseph J. Mackel ◽  
Jaleesa M. Garth ◽  
MaryJane Jones ◽  
Diandra A. Ellis ◽  
Jonathan P. Blackburn ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Periodic Acid ◽  
Acute Infection ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Allergic Airway Inflammation ◽  
Lung Edema ◽  
Periodic Acid Schiff ◽  
Wide Range ◽  
Type 2 Inflammation

Exposure to fungi can result in a wide range of comorbidities depending on the immune status of the host. Chronic exposure and reactivity to fungi such as Aspergillus fumigatus can result in conditions such as severe asthma with fungal sensitization (SAFS) or allergic bronchopulmonary aspergillosis (ABPA). However, the pathophysiology of SAFS and ABPA are not well understood. Here, we report that the chitinase-like protein YKL-40 is elevated in lung lavage fluid from human asthmatics that are sensitized to fungi. Initial studies demonstrated that mice deficient in the murine ortholog of YKL-40, breast regression protein-39 (BRP-39, chitinase-3-like 1, Chi3l1), were not more susceptible to acute infection with A. fumigatus. However, in an experimental model of fungal-associated allergic airway inflammation (fungal asthma), Chi3l1-/- mice had significantly increased airway hyperresponsiveness (AHR). Surprisingly, increased AHR in Chi3l1-/- mice occurred in the presence of significantly lower type 2 responses (decreased eosinophil numbers and decreased IL-4, IL-5, IL-33, CCL17 and CCL22 levels), although type 1 and type 17 responses were not different. Increased AHR was not associated with differences in Periodic-acid-Schiff staining of lung tissue, differences in the expression of Muc5ac and Clca3, nor differences in lung edema. Bone marrow chimera studies revealed that the presence of BRP-39 in either the hematopoietic or non-hematopoietic compartment was sufficient for controlling AHR during fungal asthma. Collectively, these results indicate that BRP-39 protects against AHR during fungal asthma despite contributing to type 2 inflammation, thus highlighting an unexpected protective role for BRP-39 in allergic fungal asthma.

scholarly journals IFITM proteins drive type 2 T helper cell differentiation and exacerbate allergic airway inflammation

2018 ◽  
Vol 49 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Diana C. Yánez ◽  
Hemant Sahni ◽  
Susan Ross ◽  
Anisha Solanki ◽  
Ching-In Lau ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper

scholarly journals The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Morris Nechama ◽  
Jeahoo Kwon ◽  
Shuo Wei ◽  
Adrian Tun Kyi ◽  
Robert S. Welner ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Type 2 Immunity

scholarly journals Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin-induced allergic airway inflammation

Immunology ◽  
2014 ◽  
Vol 142 (2) ◽  
pp. 202-215 ◽  
Author(s):  
Wenwei Zhong ◽  
Wen Su ◽  
Yanjie Zhang ◽  
Qi Liu ◽  
Jinhong Wu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Type 2 Immunity ◽  
Helper Type

scholarly journals Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway inflammation

2018 ◽  
Vol 48 (11) ◽  
pp. 1838-1850 ◽  
Author(s):  
Jiajia Lv ◽  
Qianying Yu ◽  
Jie Lv ◽  
Caixia Di ◽  
Xiaoliang Lin ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Epithelial ◽  
Type 2 Immunity

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 An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products

2020 ◽  
Vol 12 (540) ◽  
pp. eaay0605 ◽  
Author(s):  
Marta de los Reyes Jiménez ◽  
Antonie Lechner ◽  
Francesca Alessandrini ◽  
Sina Bohnacker ◽  
Sonja Schindela ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Mitogen Activated Protein Kinase ◽  
Metabolic Enzyme ◽  
Prostaglandin E ◽  
Lipoxygenase Pathway ◽  
Anti Inflammatory ◽  
Type 2 Inflammation ◽  
Allergy And Asthma

Eicosanoids are key mediators of type-2 inflammation, e.g., in allergy and asthma. Helminth products have been suggested as remedies against inflammatory diseases, but their effects on eicosanoids are unknown. Here, we show that larval products of the helminth Heligmosomoides polygyrus bakeri (HpbE), known to modulate type-2 responses, trigger a broad anti-inflammatory eicosanoid shift by suppressing the 5-lipoxygenase pathway, but inducing the cyclooxygenase (COX) pathway. In human macrophages and granulocytes, the HpbE-driven induction of the COX pathway resulted in the production of anti-inflammatory mediators [e.g., prostaglandin E2 (PGE2) and IL-10] and suppressed chemotaxis. HpbE also abrogated the chemotaxis of granulocytes from patients suffering from aspirin-exacerbated respiratory disease (AERD), a severe type-2 inflammatory condition. Intranasal treatment with HpbE extract attenuated allergic airway inflammation in mice, and intranasal transfer of HpbE-conditioned macrophages led to reduced airway eosinophilia in a COX/PGE2-dependent fashion. The induction of regulatory mediators in macrophages depended on p38 mitogen-activated protein kinase (MAPK), hypoxia-inducible factor-1α (HIF-1α), and Hpb glutamate dehydrogenase (GDH), which we identify as a major immunoregulatory protein in HpbE. Hpb GDH activity was required for anti-inflammatory effects of HpbE in macrophages, and local administration of recombinant Hpb GDH to the airways abrogated allergic airway inflammation in mice. Thus, a metabolic enzyme present in helminth larvae can suppress type-2 inflammation by inducing an anti-inflammatory eicosanoid switch, which has important implications for the therapy of allergy and asthma.

scholarly journals Androgen signaling negatively controls group 2 innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1581-1592 ◽  
Author(s):  
Sophie Laffont ◽  
Eve Blanquart ◽  
Magali Savignac ◽  
Claire Cénac ◽  
Gilles Laverny ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Allergic Airway Inflammation ◽  
Innate Lymphoid Cells ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Peripheral Tissues ◽  
Group 2

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33–driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33–mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33–driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.

scholarly journals Role of the phosphoinositide 3-kinase p110δ in generation of type 2 cytokine responses and allergic airway inflammation

2007 ◽  
Vol 37 (2) ◽  
pp. 416-424 ◽  
Author(s):  
Baher F. Nashed ◽  
Tingting Zhang ◽  
Monther Al-Alwan ◽  
Ganesh Srinivasan ◽  
Andrew J. Halayko ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Cytokine Responses ◽  
Phosphoinositide 3 Kinase
Sign in / Sign up

Export Citation Format

Share Document