Mouse resident lung eosinophils are dependent on <scp>IL</scp>‐5

Dolitzky, Avishay; Grisaru‐Tal, Sharon; Avlas, Shmuel; Hazut, Inbal; Gordon, Yaara; Itan, Michal; Munitz, Ariel

doi:10.1111/all.15362

Cited by 11 publications

(8 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in contrast to a previous report, we observed at best only minor expression of CD62L in rEOS from naïve mice or in response to 4× HDM exposure 12 . CD62L expression in rEOS seems to be variable, as a recent report did not find CD62L expression in rEOS, similar to our observation 45 . Further, we found strong induction of CD11c in iEOS present in the airways, 27,28 the lung tissue and to a lower extent in the mLN.…”

Section: Discussionsupporting

confidence: 51%

“…12 CD62L expression in rEOS seems to be variable, as a recent report did not find CD62L expression in rEOS, similar to our observation. 45 Further, we found strong induction of CD11c in iEOS present in the airways, 27,28 the lung tissue and to a lower extent in the mLN. Thus, our findings identify CD11c as an excellent marker to discriminate iEOS from rEOS.…”

Section: Discussionmentioning

confidence: 53%

See 1 more Smart Citation

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

Wiese

Duhn

Korkmaz

et al. 2023

Allergy

View full text Add to dashboard Cite

Background Pulmonary eosinophils comprise at least two distinct populations of resident eosinophils (rEOS) and inflammatory eosinophils (iEOS), the latter recruited in response to pulmonary inflammation. Here, we determined the impact of complement activation on rEOS and iEOS trafficking and function in two models of pulmonary inflammation. Methods BALB/c wild‐type and C5ar1−/− mice were exposed to different allergens or IL‐33. Eosinophil populations in the airways, lung, or mediastinal lymph nodes (mLN) were characterized by FACS or immunohistochemistry. rEOS and iEOS functions were determined in vivo and in vitro. Results HDM and IL‐33 exposure induced a strong accumulation of iEOS but not rEOS in the airways, lungs, and mLNs. rEOS and iEOS expressed C3/C5 and C5aR1, which were significantly higher in iEOS. Initial pulmonary trafficking of iEOS was markedly reduced in C5ar1−/− mice and associated with less IL‐5 production from ILC2 cells. Functionally, adoptively transferred pulmonary iEOS from WT but not from C5ar1−/− mice‐induced airway hyperresponsiveness (AHR), which was associated with significantly reduced C5ar1−/− iEOS degranulation. Pulmonary iEOS but not rEOS were frequently associated with T cells in lung tissue. After HDM or IL‐33 exposure, iEOS but not rEOS were found in mLNs, which were significantly reduced in C5ar1−/− mice. C5ar1−/− iEOS expressed less costimulatory molecules, associated with a decreased potency to drive antigen‐specific T cell proliferation and differentiation into memory T cells. Conclusions We uncovered novel roles for C5aR1 in iEOS trafficking and activation, which affects key aspects of allergic inflammation such as AHR, ILC2, and T cell activation.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 53%

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

Wiese

Duhn

Korkmaz

et al. 2023

Allergy

View full text Add to dashboard Cite

show abstract

“…However, this idea has recently been challenged with evidence that anti-IL-5 treatment depletes all populations of eosinophils. 18 Whether this distinction would result in a different pattern of adverse effects in patients remains unclear, notably as the patient who developed RA in this report was receiving mepolizumab.…”

Section: Discussionmentioning

confidence: 93%

Anti-IL-5 biologics and rheumatoid arthritis: a single-centre 500 patient year exposure analysis

Dean,

Clifton,

Salman

et al. 2023

RMD Open

View full text Add to dashboard Cite

ObjectiveThe increasing use of biological therapies has led to the paradoxical finding that monoclonal antibody therapy for one inflammatory disease can sometimes induce another inflammatory disease. Recently, the use of anti-IL-5 (IL, interleukin) antibody therapies for severe asthma has been associated with the onset of rheumatoid arthritis (RA) and other inflammatory rheumatological disease. We undertook this audit to identify the prevalence of this finding across a large clinical cohort of patients receiving anti-IL-5 therapy.MethodsAll patients currently receiving mepolizumab or benralizumab for severe asthma across the Leeds Teaching Hospitals NHS Trust’s (LTHT) Respiratory Service were included. Electronic records for each patient were searched to identify clinical and biochemical manifestations of inflammatory rheumatological disease following the initiation of anti-IL-5 therapy.Results142 patients, with a mean duration of 3.5 years on therapy, were included (89 mepolizumab, 53 benralizumab). 17 patients developed new arthralgias (nine mepolizumab, eight benralizumab), however only one of these patients (on mepolizumab) had raised acute phase reactants and newly positive anti-CCP antibody (ACPA) and rheumatoid factor and was the only patient to receive a formal diagnosis of RA.ConclusionAlthough ACPA positive RA has now been reported in a handful of case reports, we noted a very low rate of evolution into RA or inflammatory arthritis, at least in the short-medium term under anti-IL-5 therapy. This challenges the emerging suggestion that anti-IL-5 biologics may be triggering RA.

show abstract

“…Except for a recently published study in mice [ 27 ], the available evidence points to iEOS being the only subset dependent on IL-5 [ 13 ]. This is important, as treatment with anti-IL-5 or anti-IL-5Ra can influence the two subsets in a different way, probably eliminating iEOS without affecting rEOS.…”

Section: Discussionmentioning

confidence: 99%

Identification of Two Eosinophil Subsets in Induced Sputum from Patients with Allergic Asthma According to CD15 and CD66b Expression

Curto

Mateus-Medina

Crespo-Lessmann

et al. 2022

IJERPH

View full text Add to dashboard Cite

Two subsets of eosinophils have been described: resident eosinophils with homeostatic functions (rEOS) in healthy subjects and in patients with nonallergic eosinophilic asthma, and inflammatory eosinophils (iEOS) in blood and lung samples from patients with allergic asthma. We explored if it would be possible to identify different subsets of eosinophils using flow cytometry and the gating strategy applied to induced sputum. We conducted an observational cross-sectional single-center study of 62 patients with persistent allergic asthma. Inflammatory cells from induced sputum samples were counted by light microscopy and flow cytometry, and cytokine levels in the supernatant were determined. Two subsets of eosinophils were defined that we call E1 (CD66b-high and CD15-high) and E2 (CD66b-low and CD15-low). Of the 62 patients, 24 were eosinophilic, 18 mixed, 10 paucigranulocytic, and 10 neutrophilic. E1 predominated over E2 in the eosinophilic and mixed patients (20.86% vs. 6.27% and 14.42% vs. 4.31%, respectively), while E1 and E2 were similar for neutrophilic and paucigranulocytic patients. E1 correlated with IL-5, fractional exhaled nitric oxide, and blood eosinophils. While eosinophil subsets have been identified for asthma in blood, we have shown that they can also be identified in induced sputum.

show abstract

Mouse resident lung eosinophils are dependent on IL‐5

Cited by 11 publications

References 6 publications

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

C5aR1 activation in mice controls inflammatory eosinophil recruitment and functions in allergic asthma

Anti-IL-5 biologics and rheumatoid arthritis: a single-centre 500 patient year exposure analysis

Identification of Two Eosinophil Subsets in Induced Sputum from Patients with Allergic Asthma According to CD15 and CD66b Expression

Contact Info

Product

Resources

About