# Role of Aiolos in eosinophilic Asthma

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $397,500

## Abstract

Abstract
Eosinophils are circulating leukocytes that contribute to a variety of diseases due to their pro-
inflammatory function. Evidence is now accumulating linking eosinophils and their selective
cytokines (eotaxins and IL-5) to Alzheimer's disease (AD) and related cognitive decline
disorders. For example, eotaxin-1/CCL11 reversibly inhibits neural progenitor cell proliferation in
vitro in isolated cells, neurospheres, and hippocampal cultures. Additionally, administration of
plasma of aging mice or eotaxin-1/CCL11 to young mice decreases adult neurogenesis and
impairs memory and learning, establishing a major potential role for this chemokine in the age-
related decline of hippocampal function. There is even genetic evidence linking the CCL11 locus
with susceptibility for early onset AD. Further support for the connection between eosinophils
and AD is rendered by the association of IL-5 with the amyloid deposits of the brain tissues of
AD patients. Human amylin has been shown to inhibit IL-5–mediated eosinophil survival and
increase the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) by
eosinophils following stimulation with calcium ionophore A23187. On the basis of these data, we
have formulated the central hypothesis that CCL11 elicits increasing capacity to activate
eosinophils as a function of the age of mice and man and that the mechanism involves
an epigenetic response associated with histone 3 lysine 27 acetylation (H3K27ac). We will
test the primary hypothesis by examining CCL11-mediated human and murine eosinophil
activation and H3K27ac as a function of the age of the eosinophil donor and eosinophil lifespan.
The studies proposed in this supplementary grant request are expected to advance our
understanding of the emerging linkage between inflammation and aging. The results are
expected to lay the foundation for understanding the association of eotaxin/CCL11 with
cognitive decline, including Alzheimer's disease, which will hopefully be pursued in a future NIH
R01 grant application. These results have potential direct implications for patients as there are a
series of emerging biological agents that directly target eosinophils and their associated
molecules, including antibodies against CCL11/eotaxin (bertalizumab) and IL-5 (benralizumab,
antolamib, mepolizumab, and reslizumab).

## Key facts

- **NIH application ID:** 10123507
- **Project number:** 3R01AI130033-04S1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Marc E. Rothenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,500
- **Award type:** 3
- **Project period:** 2017-03-16 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123507

## Citation

> US National Institutes of Health, RePORTER application 10123507, Role of Aiolos in eosinophilic Asthma (3R01AI130033-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123507. Licensed CC0.

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