Credits: None available.
Chronic unpredictable stress exacerbates allergic airway inflammation in mice
G. Dragunas*1,2,3, M.A. de Oliveira1, W. T. de Lima1, R. Gosens2,3, C.D. Munhoz1
1- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo
2- Department of Molecular Pharmacology, University of Groningen
3 - Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen
It is accepted that psychological stress can lead to asthma exacerbations (1). Amid COVID-19 pandemic, exposure to chronic and, hence, deleterious forms of psychological stress has become usual. Stress can be classically defined as a real or potential threat to one’s homeostasis, generating physiological responses, such as HPA and SNS axis activation (2). Studies in the literature are widely in agreement that stress induces neuroplastic changes in psychiatric disorders and some suggest that this might also happen in conditions as asthma (3,4). However, the knowledge concerning how stress increases asthma severity and if neuronal mechanisms play a role are scarce.
We applied a 12 days chronic unpredictable stress (CUS) paradigm in OVA sensitized mice followed by two daily OVA challenges to induce allergic airway inflammation. 24h after the last challenge, mice had lung functional parameters analyzed, were euthanized, bronchoalveolar lavage collected and the lungs and dorsal root ganglia (DRG) harvested. The tissues were submitted to histological and molecular assays.
Exposure to 12 day-CUS increased cellular content recovered in BAL. This was paired to increased p65 NF-kB phosphorylation, TRPV1 and P2X3 receptors expression in DRG, but not in the lungs. Exposure to CUS before acute challenge to two OVA aerosol challenges significantly increased recovered cells in BAL. Opposite outcomes were observed after a single acute restraint stress (RS), as reduced cellularity in BAL and diminished airway resistance to methacholine. OVA+CUS group displayed increased NF-kB signaling and VCAM expression in the lungs.
Exposure to chronic stress can lead to allergic airway inflammation exacerbation in mice, whereas previous acute stress led to inflammation mitigation. Future experiments will determine differential cytokine and neurotrophic factor expression in the lungs and changes in innervation in the airways in response to chronic stress.
1. Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain Behav Immun. 2007;21(8):993–9.
2. de Kloet ER, Joëls M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6(6):463–75.
3. Dragunas G, Woest ME, Nijboer S, Bos ST, van Asselt J, de Groot AP, et al. Cholinergic neuroplasticity in asthma driven by TrkB signaling. FASEB J. 2020;34(6):7703–17.
4. Undem BJ, Taylor-Clark T. Mechanisms underlying the neuronal-based symptoms of allergy. J Allergy Clin Immunol. 2014;133(6):1521–34.
Credits: None available.
Epidermal growth factor receptor in airway remodeling during allergic airway disease – divergent roles during early life and adulthood?
H. Stölting, S. A. Walker, M. C. Zarcone, F. Puttur, S. Saglani, C. M. Lloyd
National Heart and Lung Institute, Imperial College London - London (United Kingdom)
Airway remodelling is a key pathological feature of paediatric and adult asthma, but the underlying mechanisms remain poorly understood. However, their elucidation is crucial, since lung function deficits established in children with asthma persist into adulthood. Epidermal growth factor receptor (EGFR) was shown to be overexpressed in paediatric and adult asthmatics. In addition, several in vivo studies using rodent models of allergic airway disease (AAD) have described a role for EGFR signalling in driving impaired lung function and airway remodelling in adult animals. Here, we aimed to study the role of EGFR in early life AAD.
Bronchial epithelial cells from non-asthmatic children cultured at air-liquid interface were shown to exhibit high mRNA levels for EGFR and its ligands. Exposure of these cells to the allergen house dust mite induced EGFR activation dose-dependently, as measured by Y1068 phosphorylation. qPCR analysis of flow-sorted murine lung cell populations during postnatal development similarly showed high EGFR expression in murine lung epithelial cells from neonatal and adult mice, and lung epithelial EGFR expression was confirmed by flow cytometry. Finally, a pharmacological inhibitor was used to block EGFR signalling in a neonatal model of AAD. Preliminary findings indicate that EGFR inhibition in neonatal mice resulted in worsened lung function, as measured by a 2-fold increase in airway resistance (AUC), without affecting overall inflammation, a finding we did not observe in a corresponding adult AAD model.
These results indicate that EGFR is present in lungs at all stages of life and that, in contrast to its widely described pathogenic contribution to airway remodelling of adult animals, signalling through EGFR may play a protective role during early life AAD.
Credits: None available.
Cannabis compounds have both anti-inflammatory and pro-inflammatory activities in lung epithelial and macrophages while substantially increasing phagocytosis in vitro
Seegehalli M Anil1+, Nurit Shalev1+, Ajjampura C Vinayaka1+, Stalin Nadarajan1+, Dvory Namdar1, Eduard Belausov1, Irit Shoval2, Karthik Ananth Mani3, Guy Mechrez3, Hinanit Koltai1*
1 Institute of Plant Science, Agriculture Research Organization, Volcani Center, Rishon LeZion 7528809, Israel
2 The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
3 Institute for Postharvest and Food Science, Agriculture Research Organization, Volcani Center, Rishon LeZion 7528809, Israel
+ These authors contributed equally to this work
Cannabis sativa is used worldwide for medical purposes and is known to have anti-inflammatory activity, yet the potential for use of C. sativa compounds against Coronavirus disease 2019 (COVID-19)-like inflammation is unexplored. The purpose of this study was to examine the anti-inflammatory activity of cannabis on markers of immune responses associated with COVID-19 inflammation. An extract fraction from high cannabidiol (CBD) cannabis strain (FCBD) substantially reduced dose dependently interleukin 6 (IL-6) and interleukin-8 (IL-8) levels in an alveolar epithelial (A549) cell line. FCBD contained CBD, cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and phytocannabinoid standards that compose FCBD (FCBD:std) reduced in a dose dependent way IL-6, IL-8, C-C Motif Chemokine Ligands (CCLs) 2 and 7 in the A549 cell line. It also reduced expression of angiotensin I converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. Treatment with FCBD induced macrophage (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased expression of scavenger receptor CD36 and that of type II receptor for the Fc region of IgG (FcγRII). FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std, while maintaining the anti-inflammatory activity in alveolar epithelial cells, led to reduced pro-inflammatory IL secretion in macrophages in comparison to FCBD and reduced level of phagocytosis. The phytocannabinoid mixture may show superior activity for reduction of lung inflammation over that of the cannabis fraction. Yet, as for now, users and healthcare personnel should avoid the use of cannabis for COVID-19 prevention or treatment.
Credits: None available.
Glucagon-like Peptide-1 Receptor Agonists decrease type-2 biomarker in asthma
Dinah Foer1,2, Patrick Beeler3, Jing Cui1,2, Joshua A. Boyce1,2, Elizabeth Karlson1,2, David W. Bates1,2, Katherine Cahill4
1Brigham and Women's Hospital, 2Harvard Medical School, Boston, MA, 3University Hospital of Zurich, Zurich, Switzerland, 4Vanderbilt University Medical Center, Nashville, TN.
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are approved for the treatment of type II diabetes mellitus (DMII) and obesity. In murine models, GLP-1RA inhibit allergen- and viral-induced airway inflammation including airway interleukin (IL)-33 release, IL-13 and mucus production and hyperresponsiveness. Observational patient data supports an association between GLP-1RA use and decreased asthma exacerbations in patients with asthma and DMII. We hypothesized that GLP-1RA would decrease biomarkers pertinent to airway inflammation pathways in patients with asthma. To test this hypothesis, we obtained serum samples from adults with asthma and comorbid DMII in the Partners HealthCare Biobank treated with (N=43) or without a GLP-1RA (N=119) at the time of sample collection. Demographics, body mass index, asthma severity, glucose control, and comorbidities, confirmed by electronic health record chart review were extracted and a propensity score calculated based on GLP-1RA use included as a covariate in a logistic regression model. Serum periostin, total IgE, IL-6, IL-8, IL-33 and sST2 levels were measured. Periostin (Padi=.0006) was significantly decreased in GLP-1RA users than non-GLP-1RA users which included use of basal insulin, SGLT-2 inhibitors or sulfonylureas. There were no significant differences in total IgE (Padj =.12), IL-6 (Padj =.62), IL-8 (Padj =.41), sCD163 (Padj=.53), IL-33 (Padj =.91), and sST2 (Padj =.90). Periostin results were robust across asthma severity and gender subgroup analyses. Serum periostin, a known systemic biomarker of Type (T)2 cytokines IL-4 and IL-13 in airway inflammation, is significantly and selectively decreased in adults with asthma and comorbid DMII treated with GLP-1RAs. Our results support a role for GLP-1R signaling in airway inflammation and point to periostin as a possible biomarker for therapeutic use of GLP-1RAs in asthma.
Funding: NIH AI118804, Brigham and Women’s Hospital Department of Medicine Innovation Evergreen Award, Brigham Research Institute Pilot Award
Credits: None available.
ADAR-mediated editing of miR-200b-3p in airway cells is associated with moderate-to-severe asthma
Magnaye KM(1), Naughton KA(1), Huffman J(1), Hogarth DK(2), Naureckas ET(2), White SR(2), Ober C(1)
1. Department of Human Genetics, University of Chicago, Chicago, IL
2. Department of Medicine, University of Chicago, Chicago, IL
Asthma is a chronic lung disease characterized by persistent airway inflammation and bronchial hyperresponsiveness. Altered microRNA-mediated gene silencing in bronchial epithelial cells has been reported in asthma, yet microRNA adenosine to inosine (A-to-I) editing in asthma remains unexplored. We performed the first genome-wide analysis of ADAR-mediated microRNA editing using microRNA-seq in primary bronchial epithelial cells from 142 adult asthma cases and non-asthma controls. Of 19 A-to-I edited sites detected in these microRNAs, 16 were in seed regions. Four of the 16 edited sites were observed in >10 individuals and were tested for differential editing (% A-to-I) between groups. One site at position 5 of miR-200b-3p was edited less frequently in asthma cases compared to controls (P = 0.013). A-to-I editing of this site was then compared between asthma severity groups (mild, moderate and severe) based on lung function and medication use. The moderate (P = 0.037) and severe (P = 0.00031), but not mild (P = 0.77), asthma cases had significantly less A-to-I editing of the 5th position of miR-200b-3p compared to controls. Bioinformatic prediction revealed 232 in silico target genes of the edited miR-200b-3p, which were enriched for both IL-4 and interferon gamma signaling pathways and included the SOCS1 (suppressor of cytokine signaling 1) gene. SOCS1 was more highly expressed in moderate (P = 0.017) and severe (P = 0.0054) asthma cases compared to controls. Moreover, both miR-200b-3p editing and SOCS1 were associated with BAL eosinophil levels and an epithelial cell signature of Type 2 asthma. Overall, reduced ADAR-mediated editing of the 5th position of miR-200b-3p in lower airway cells from moderate-to-severe asthmatics may lead to overexpression of a centrally important negative regulator of cytokine signaling, SOCS1. We proposed ADAR-mediated editing as an epigenetic mechanism contributing to features of moderate-to-severe asthma in adulthood. Supported by U19 AI095230. KMM is supported by F31 HL143891.
Credits: None available.
MicroRNA regulation of airway mucus production
Siddiqui S*1,2, Johansson K*1,2,3, Joo A1,2, Bonser LR4,5, Koh KD4,5, Le Tonqueze O4,5, Bolourchi S1,2, Bautista RA1,2, Zlock L6, Roth TL3,7,8,9, Marson A3,9,10,11,12,13, Bhakta NR1, Ansel KM2,3, Finkbeiner WE6, Erle DJ4,5, Woodruff PG1,2,5
1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, 2Sandler Asthma Basic Research Center, 3Department of Microbiology and Immunology, 4Lung Biology Center, 5Cardiovascular Research Institute, 6Department of Pathology, 7Biomedical Sciences Graduate Program, 8Diabetes Center, 9Innovative Genomics Institute, University of California, Berkeley, 10J. David Gladstone Institutes, 11Department of Medicine, Division of Infectious Diseases, 12Parker Institute for Cancer Immunotherapy and 13Chan Zuckerberg Biohub, San Francisco, CA, USA
* Equal contribution
Rational: Interleukin (IL)-13-induced goblet cell metaplasia contributes to airway remodeling and pathological mucus hypersecretion in asthma. MicroRNAs (miRNAs) are a distinct class of noncoding RNAs, about 20-22 nucleotides long, that mediate sequence-specific repression of target mRNAs. Cellular responses are modulated by miRNAs but their role in mucus regulation is largely unexplored. We hypothesized that airway epithelial miRNAs play a role in IL-13-induced mucus regulation.
Methods: We performed CRISPR/Cas9-editing of primary human bronchial epithelial cells (HBECs) to target a specific miRNA candidate, miR-141, by delivery of MIR141-targeting guide RNAs (gRNA) via electroporation. HBECs that received MIR141 gRNAs or non-targeting gRNA control were differentiated at air-liquid-interface (ALI) and epithelial mucus was induced by IL-13 stimulation.
Results: miR-141, a member of the miR-141/200 family, was identified as one of the most highly expressed miRNAs in human airway epithelium by miRNA sequencing. Analysis of bronchial brushings from asthmatic subjects revealed that miR-141 is reduced at baseline in asthma but is induced shortly after airway allergen challenge. Knock down of miR-141 resulted in decreased goblet cells frequency, intracellular MUC5AC and total secreted mucus. These effects correlated with a reduction in a goblet cell gene expression signature and enrichment of a basal cell gene expression signature defined by single cell RNA sequencing. Furthermore, intranasal administration of a sequence-specific miR-141 inhibitor in mice decreased Aspergillus-induced secreted mucus and mucus-expressing cells in the lung, and reduced airway hyper-responsiveness without affecting cellular inflammation.
Conclusions: We have identified a miRNA that regulates pathological airway mucus production in human cells and in mice and is amenable to therapeutic manipulation through an inhaled route.
Credits: None available.
Deficient inflammasome activation permits an exaggerated asthma phenotype in response to early-life RV-C15 infection
Mingyuan Han1, Claudia Stroupe1, Tomoko Ishikawa1, J. Kelley Bentley1 and Marc B. Hershenson1,2
Departments of 1Pediatrics and 2Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109
Background: Early-life wheezing-associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV-A1B infection of six day-old immature mice causes an asthma-like phenotype dependent on IL-13-producing type 2 innate lymphoid cells (ILC2s) (Hong J et al. J Allergy Clin Immunol 2014). RV species C (RV-C) has been associated with severe respiratory illnesses in children and adults and is more likely to occur in children with a history of asthma or who develop asthma. We therefore examined the effect of RV-C15 infection in immature mice.
Methods: Six day-old wild type and TLR2-/- mice were inoculated with sham, RV-A1B, or RV-C15. Selected mice were treated recombinant IL-1β. Cultured macrophages derived from human peripheral blood monocytes, human THP-1 cells and mouse bone marrow were also infected with sham, RV-A1B or RV-C15.
Results: As shown previously, RV-A1B infection of six day-old mice induced type 2 cytokine expression, ILC2 expansion and mucous metaplasia. However, compared to RV-A1B infection, RV-C15 infection induced an exaggerated asthma phenotype, with significantly increased mRNA expression of Il5, Il13, Il25, Il33, Muc5ac, Muc5b and Gob5, increased lung lineage-negative CD25+CD127+ST2+ ILC2s, and increased PAS and Muc5ac immunostaining. Viral load and induction of pro-inflammatory type 1 cytokines were not different between the two viruses.
We have shown that IL-1β, a product of inflammasome activation, attenuates airway type 2 cytokine responses (Han M et al. Allergy. 2020). We therefore examined the effects of RV-C15 and RV-A1B on inflammasome priming and activation. Infection of six day-old mice with RV-C15 and RV-A1B induced an equal amount of inflammasome priming (pro-IL-1β and NLRP3), but RV-C15-induced inflammasome activation (IL-1β and caspase-1 p12) was reduced compared to RV-A1B. A similar deficiency of inflammasome activation was found in cultured macrophages. Both viruses induced TLR2-dependent inflammasome priming, but less viral genomic RNA was detected in RV-C15 infected cells. Finally, treatment with IL-1β decreased RV-C-induced type 2 cytokine and mucus-related gene expression but not viral load or expression of pro-inflammatory type 1 cytokines, consistent with the notion that inflammasome activation has a suppressive effect on the asthma phenotype.
Conclusions: Infection of immature mice with RV-C induces an enhanced asthma phenotype compared to RV-A. Interaction of RV-C with airway macrophages triggers inflammasome priming, but inflammasome activation and IL-1β are deficient, thereby permitting exaggerated type 2 inflammation and mucous metaplasia following early-life RV-C infection.
Credits: None available.
CD4 Tissue Resident Memory T Cells Promote Inflammatory Pathways Associated with Asthma
Nathan Schoettler1, Anne I Sperling1, Carole Ober2
1University of Chicago, Department of Medicine; 2University of Chicago, Department of Human Genetics
Activated CD4 T cells drive asthma pathogenesis through distinct cytokine and inflammatory pathways that have been linked to asthma phenotypes. These include Th2 and Th17 cytokines and IL-2, which drives antigen-specific T cell proliferation. However, the specific subset(s) of human lung CD4 T cells that contributes to these responses and how these T cells are activated is unknown. Features of human CD4 memory T cells differ between the lung and other sites, including higher expression of innate immune receptors, different proportion of memory subsets and distinct T cell receptor repertoires. We have characterized the responses of human lung CD4 effector memory (TEM) and tissue resident memory (TRM) T cell subsets to innate stimuli (lipopolysaccharide and poly-I:C, separately) and T cell receptor (TCR)-specific activation (anti-CD3/anti-CD28) in a total lung leukocyte cell culture model from 10 lung donors. After 20 hours of treatment, CD4 TEM and TRM T cells were sorted and RNA was extracted and sequenced for comparison of the transcriptional differences between cell types and between treatments. While there were no differences in gene expression responses between CD4 TEM and TRM cells after lipopolysaccharide or poly-I:C treatment at a false discovery rate of 5%, 424 genes were differentially expressed between CD4 TEM and TRM cells after anti-CD3/anti-CD28 treatment. Genes with higher expression in CD4 TRM cells included IL2, Th2 cytokines (IL4, IL13 and IL5) and the Th17 cytokine IL17A. Our results demonstrate that human CD4 TRM cells promote asthma-relevant responses after TCR-specific activation and that innate stimulation alone or TCR-specific activation of CD4 TEM cells does not activate these responses.
Credits: None available.
Obesity dysregulates immunometabolic status in pediatric asthma and impacts vaccine responses
Sarah E. Henrickson1,2, Peyton Conrey2, Sasikanth Manne1,3, , Samir Sayed2, Kaitlin C. O’Boyle3 Bertram Bengsch1,† , Ting Qian4, Ramin S. Herati1,5†††, Laura A. Vella1,6, Allison R. Greenplate1,3, Sam J. McCright1,7, Cécile Alanio1,3, 12, Frank Mentch11, Kenneth E. Schmader8, Christopher F. Pastore9, Li-Yin Hun9, Scott E. Hensley1,10, De’Broski Herbert9, Aaron J. Masino4, Jorge Henao-Mejia1,7, Hakon Hakonarson11, Joshua D. Rabinowitz12, Susan E. Coffin6 and E. John Wherry1,3,12
1Institute for Immunology, University of Pennsylvania, Philadelphia, PA.
2Division of Allergy-Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA.
3Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA.
4Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia, Philadelphia, PA.
5Department of Medicine, University of Pennsylvania Perelman School of Medicine
6Division of Infectious Disease, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA.
7Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA.
8Division of Geriatrics, Department of Medicine, Duke University Medical Center and Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC.
9School of Veterinary Medicine, Department of Pathobiology, University of Pennsylvania, Philadelphia. PA
10Department of Microbiology, University of Pennsylvania, Philadelphia, PA.
11Center for Applied Genomics, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA.
12Parker Institute for Cancer Immunotherapy at University of Pennsylvania
13Department of Chemistry, Princeton University, Princeton, NJ.
†1Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Faculty of Medicine, Freiburg, Germany, and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
††Department of Medicine, New York University, Grossman School of Medicine, New York City, NY.
Asthma and obesity are two of the most common chronic childhood diseases worldwide, with dramatically increasing prevalence over the last few decades. These diseases impact morbidity and mortality and strain health care systems financially. Asthma risk increases as body mass index (BMI) increases, suggesting a pathophysiological link. Both asthma and obesity are independently linked to altered immune status, however, it remains unclear how these diseases converge to affect pediatric immune function. To address this question, we investigated the immunometabolic profile in obese asthmatic (OA), non-obese asthmatic (A), obese non-asthmatic (O), and healthy control (HC) children using mass cytometry, serum metabolomics, cytokine analysis and clinical history. This multi-modal approach revealed two major forms of immune dysfunction in pediatric allergic OA: altered baseline T cell activation state (exhaustion-like) and increased type 2 immunity. OA had increased Th2 differentiation and decreased Th17 differentiation and these changes were associated with altered blood metabolites, including increased glutamate and decreased acetate. A mouse model of OA confirmed increased exhausted-like CD8 T cells compared to A and HC mice. Finally, immunometabolic dysregulation and altered T cell activation status in O and OA patients was linked to prolonged retention of humoral vaccine responses. These insights into the mechanistic links between metabolic alterations and immune dysfunction in OA may improve understanding of the severe asthma exacerbations secondary to viral upper respiratory tract infections seen in OA and provide opportunities for novel therapeutic approaches.
Credits: None available.
RNA binding protein HuR posttranscriptionally regulates CD4+ T cell inflammatory gene expression in asthma
Ulus Atasoy1, Fatemeh Fattahi1, Jason Ellis1, Kristin Bahleda1, Nerissa Reister1, Njira Lugogo1,
1 University of Michigan, Ann Arbor, MI.
Due to poor correlation between steady-state mRNA levels and protein product, transcriptomic analyses may miss critical genes controlling inflammation. Many genes are regulated posttranscriptionally at levels of mRNA stability and translation by RNA-binding proteins (RBPs) and miRNAs, however this is not well understood. Pro-inflammatory genes which play pivotal roles in airway inflammation usually have labile mRNA transcripts and are regulated posttranscriptionally. Using novel RIP-Seq methods, we have uncovered how RBP HuR (elavl1) regulates key genes involved in CD4+ Th subset differentiation since it binds to and regulates gata3 and Th2 cytokine mRNAs. HuR regulates inflammatory genes allowing for lung inflammation in asthma. We previously demonstrated that HuR overexpression in CD4+ T cells results in increases in Th2 cytokine production. Conditional ablation of HuR in T cells (distal Lck-cre HuRfl/fl), abrogates Th2 differentiation, cytokine production and lung inflammation in ova challenge model. We hypothesized that HuR may similarly regulate lung inflammation in human asthma. We discovered that HuR protein expression is greatly increased (100%) in peripheral CD4+ T cells from asthmatics (both type 2 high and low) compared with healthy individuals. Asthmatic PBLs have increased frequency and production of both Th2/Th17 signature cytokines. Using a drug (acadesine aka AICAR) which interferes with HuR function, we show that CD4+ T cells treated with acadesine have decreases in Th2/17 cytokine expression. Taken together, these data suggest that HuR plays a permissive role in both allergen and non-allergen driven airway inflammation by regulating key genes and that interfering with its function may be a novel way to treat asthma.