Targeted deletion of Interleukin-3 results in asthma exacerbations

̈lle, Julia Ko; Zimmermann, Theodor; Krause, Alexander; Rieker, Ralf J.; Xepapadaki, Paraskevi; Zundler, Sebastian; Papadopoulos, Nikolaos G.; Finotto, Susetta

doi:10.1016/j.isci.2022.104440

Cited by 6 publications

(7 citation statements)

References 52 publications

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“…In human, it was shown that (i) sputum IL-3 secretion correlates with levels of eosinophil granule proteins and decreased lung function ( 93 ); (ii) IL-3 + BALF cells are associated with asthma severity ( 96 ) and; (iii) serum IL-3 levels are higher in patients with uncontrolled chronic asthma ( 97 ). By contrast, other studies revealed that IL-3 produced by PBMCs is associated with amelioration of asthma in pre-school children ( 31 ) and that IL-3 expression in lung tissue is not correlated with eosinophil and metachromatic cell number, airway responsiveness, or the severity of the late asthmatic response ( 95 ). Mechanistically, IL-3 was described to protect against asthma by reducing the number of innate lymphoid cell type 2 in lungs and by increasing regulatory T cell number in the airways ( 30 , 31 ).…”

Section: Il-3 In Diseasesmentioning

confidence: 89%

“…Indeed, IL-3 levels were found either increased in sputum ( 93 ) and BALF ( 94 ) of asthmatic patients, reduced in nasopharyngeal fluid of asthmatic children ( 30 ), or similar in bronchial biopsies between asthmatic and non-asthmatic patients ( 95 ). Likewise, a report showed that mice deficient for Il-3 exhibit increased pulmonary inflammation during asthma, characterized by local eosinophil infiltration and increased secretion of IgE, IL-5, and IL-13 ( 31 ). On the contrary, another study reported that Il-3 -/- mice show similar number of basophils and eosinophils in BALF as well as similar serum IgE levels when compared to control mice ( 32 ).…”

Section: Il-3 In Diseasesmentioning

confidence: 99%

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IL-3: key orchestrator of inflammation

Podolska,

Grützmann,

Pilarsky

et al. 2024

Front. Immunol.

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Interleukin (IL)-3 has long been known for its hematopoietic properties. However, recent evidence has expanded our understanding of IL-3 function by identifying IL-3 as a critical orchestrator of inflammation in a wide array of diseases. Depending on the type of disease, the course of inflammation, the cell or the tissue involved, IL-3 promotes either pathologic inflammation or its resolution. Here, we describe the cell-specific functions of IL-3 and summarize its role in diseases. We discuss the current treatments targeting IL-3 or its receptor, and highlight the potential and the limitations of targeting IL-3 in clinics.

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Section: Il-3 In Diseasesmentioning

confidence: 89%

Section: Il-3 In Diseasesmentioning

confidence: 99%

IL-3: key orchestrator of inflammation

Podolska,

Grützmann,

Pilarsky

et al. 2024

Front. Immunol.

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“…26 Nevertheless, there is also evidence that altered immune responses, by means of deficient IFNγ, are detected antenatally in infants with subsequent wheeze. 98 Epidemiological data indicate that such severe early wheezing illnesses are significantly more prevalent in atopic families 99 and cohort studies have shown that respiratory infections induce asthmalike symptoms to a greater extent in atopic asthmatics than normal controls, 100 a susceptibility also confirmed in children with severe asthma. 101 In accordance, susceptibility to respiratory infections was significantly more pronounced in atopic preschoolers than in non-atopic ones.…”

Section: Antivir Al Immune Re S P Ons E S and Suscep Tib Ilit Y Of At...mentioning

confidence: 99%

“…Interestingly, a differential humoral response has been reported in asthmatic compared with healthy controls, resulting in altered protection against different RV species 26 . Nevertheless, there is also evidence that altered immune responses, by means of deficient IFN‐γ, are detected antenatally in infants with subsequent wheeze 98 …”

Section: Antiviral Immune Responses and Susceptibility Of Atopics To ...mentioning

confidence: 99%

Bacteria and viruses and their role in the preschool wheeze to asthma transition

Papadopoulos,

Apostolidou,

Miligkos

et al. 2024

Pediatric Allergy Immunology

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Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or recurrent disease. Early‐life wheezing and asthma exacerbations are triggered by common respiratory viruses, mainly rhinoviruses (RV), and to a lesser extent, respiratory syncytial virus, parainfluenza, human metapneumovirus, coronaviruses, adenoviruses, influenza, and bocavirus. The excess presence of bacteria, several of which are part of the microbiome, has also been identified in association with wheezing and acute asthma exacerbations, including haemophilus influenza, streptococcus pneumoniae, moraxella catarrhalis, mycoplasma pneumoniae, and chlamydophila pneumonia. While it is not clear when asthma starts, its characteristics develop over time. Airway remodeling already appears between the ages of 1 and 3 years of age even prior to the presence of atopic inflammation or an asthma diagnosis. The role of genetic defect or variations hampering the airway epithelium in response to environmental stimuli and severe disease morbidity are now considered as major determinants for early structural changes. Repeated viral infections can induce and perpetuate airway hyperresponsiveness. Allergic sensitization, that often precedes infection‐induced wheezing, shifts inflammation toward type‐2, while common respiratory infections themselves promote type‐2 inflammation. Nevertheless, most children who wheeze with viral infections during infancy and during preschool years do not develop persistent asthma. Multiple factors, including illness severity, viral etiology, allergic sensitization, and the exposome, are associated with disease persistence. Here, we summarize current knowledge and developments in infection epidemiology of asthma in children, describing the known impact of each individual agent and mechanisms of transition from recurrent wheeze to asthma.

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“…1 for detailed sample selection). In addition, to test whether IL-3 levels were influenced by comorbidities, we performed sensitivity analysis in populations by excluding those diagnosed with sepsis, rheumatoid arthritis, acute lymphoblastic leukemia, asthma, multiple sclerosis, depression, and schizophrenia in medical history and medical record (total 44 participants were excluded), because previous studies have shown a strong relationship between these diseases and IL-3 [21][22][23][24][25][26][27]. In the present study, APOE4 status were grouped as carrying at least one APOE4 allele or no one APOE4 allele.…”

Section: Study Participantsmentioning

confidence: 99%

Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-β and tau pathology in Alzheimer’s disease

Wang

Sun

et al. 2022

J Neuroinflammation

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Background Dysfunction of glial cell communication is involved in Alzheimer’s disease (AD) pathogenesis, and the recent study reported that astrocytic secreted interleukin-3 (IL-3) participated in astrocyte–microglia crosstalk and restricted AD pathology in mice, but the effect of IL-3 on the pathological progression of AD in human is still unclear. Methods A total of 311 participants with cerebrospinal fluid (CSF) IL-3, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and AD biomarkers were included from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We assessed the associations of IL-3 with sTREM2 and AD biomarkers at baseline, and with cognitive change in longitudinal study. The mediation models were used to explore the potential mechanism of how IL-3 affects AD pathology. Results We found that CSF IL-3 was significantly associated with CSF sTREM2 and CSF AD core biomarkers (Aβ42, p-tau, and t-tau) at baseline, and was also markedly related to cognitive decline in longitudinal analysis. Moreover, mediation analysis revealed that CSF IL-3 modulated the level of CSF sTREM2 and contributed to tau pathology (as measured by CSF p-tau/t-tau) and subsequent cognitive decline. In addition, Aβ pathology (as measured by CSF Aβ42) affected the development of tau pathology partly by modifying the levels of CSF IL-3 and CSF sTREM2. Furthermore, the effect of Aβ pathology on cognitive decline was partially mediated by the pathway from CSF IL-3 and CSF sTREM2 to tau pathology. Conclusions Our findings provide evidence to suggest that IL-3 is linked to sTREM2 and mediates the correlation between Aβ pathology to tau pathology. It indicates that IL-3 may be a major factor in the spreading from Aβ pathology to tau pathology to cognitive impairment.

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Targeted deletion of Interleukin-3 results in asthma exacerbations

Cited by 6 publications

References 52 publications

IL-3: key orchestrator of inflammation

IL-3: key orchestrator of inflammation

Bacteria and viruses and their role in the preschool wheeze to asthma transition

Interleukin-3 is associated with sTREM2 and mediates the correlation between amyloid-β and tau pathology in Alzheimer’s disease

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