O4‐1: Reactive sulfur species are involved in the regulation of innate immunity of type 2 airway inflammation

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.

Download Full-text

Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase

Redox Biology ◽

10.1016/j.redox.2017.11.009 ◽

2018 ◽

Vol 15 ◽

pp. 74-85 ◽

Cited By ~ 68

Author(s):

Kenneth R. Olson ◽

Yan Gao ◽

Faihaan Arif ◽

Kanika Arora ◽

Shivali Patel ◽

...

Keyword(s):

Superoxide Dismutase ◽

Hydrogen Sulfide ◽

Sulfur Species ◽

Reactive Sulfur Species

Download Full-text

Follistatin-Like 1 Induces the Activation of Type 2 Innate Lymphoid Cells to Promote Airway Inflammation in Asthma

Inflammation ◽

10.1007/s10753-021-01594-w ◽

2021 ◽

Author(s):

Siyuan Huang ◽

Rong Zeng ◽

Jing Wang ◽

Xinrui Qiao ◽

Shuo Li ◽

...

Keyword(s):

Airway Inflammation ◽

Innate Lymphoid Cells ◽

Lymphoid Cells

Download Full-text

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00528.2020 ◽

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.

Download Full-text

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

European Journal of Immunology ◽

10.1002/eji.201847692 ◽

2018 ◽

Vol 49 (1) ◽

pp. 66-78 ◽

Cited By ~ 11

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

Download Full-text

Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.811600 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shigeki Katoh

Keyword(s):

Monoclonal Antibodies ◽

Airway Inflammation ◽

Th17 Cells ◽

Acute Asthma ◽

Mite Allergen ◽

Th2 Cells ◽

T Helper ◽

Th2 Cell ◽

Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

Download Full-text

The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

Journal of Education, Health and Sport ◽

10.12775/jehs.2021.11.09.071 ◽

2021 ◽

Vol 11 (9) ◽

pp. 544-549

Author(s):

Paulina Trojanowska ◽

Magdalena Chrościńska-Krawczyk ◽

Alina Trojanowska ◽

Ewa Tywanek ◽

Jakub Wronecki ◽

...

Keyword(s):

Innate Immunity ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

The Body ◽

Low Grade ◽

Intracellular Space ◽

Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

Download Full-text

Mechanism of innate immune reprogramming by a fungal meningitis pathogen

10.1101/2021.09.02.458767 ◽

2021 ◽

Author(s):

Eric V. Dang ◽

Susan Lei ◽

Atanas Radkov ◽

Hiten Madhani

Keyword(s):

Innate Immunity ◽

Fungal Pathogens ◽

Forward Genetics ◽

Alternative Activation ◽

Cytokine Signaling ◽

Alternatively Activated Macrophages ◽

Fungal Meningitis

How deadly fungal pathogens overcome mammalian innate immunity is largely unknown. Cryptococcus neoformans, the most common cause of fungal meningitis, induces a pathogenic type 2 response characterized by pulmonary eosinophilia and alternatively activated macrophages. Using forward genetics, we identified a fungal secreted protein, Cpl1, necessary and sufficient to enhance alternative activation of primary macrophages in vitro. Cpl1-enhanced polarization requires Toll-like receptor 4, a known mediator of allergen-induced type 2 responses. Cpl1 is essential for virulence, drives polarization of interstitial macrophages in vivo, and requires type 2 cytokine signaling for its impact on infectivity. C. neoformans selectively associates with polarized interstitial macrophages during infection, supporting a direct host-pathogen interaction. This work identifies a secreted effector produced by a human fungal pathogen that reprograms innate immunity to enable tissue infection.

Download Full-text