# Regulation of FcεRI function by the MS4A gene cluster

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2022 · $374,978

## Abstract

Project summary
Allergic diseases such as asthma, atopic dermatitis and food allergies collectively affect 30-40% of adults and
children in the U.S. and their prevalence is increasing. Current treatment strategies generally rely upon either
neutralizing individual mediators and/or dampening the immune response. However, targeting single mediators
in an inflammatory response only removes a fraction of the inflammatory “pool” of mediators and effective novel
therapeutics that directly and specifically target inflammatory mast cells is an unmet need. All allergic diseases
share a common feature of altered mast cell phenotype resulting in chronic hypersecretion of proinflammatory
mast cell mediators such as histamine, serotonin, leukotrienes, prostaglandins, proteases and cytokines. It is
likely that inherited genetic characteristics and environmental/epigenetic alterations play important roles in
development of this allergic mast cell phenotype. Interestingly, human linkage analysis has identified that the
gene loci 11q12-q13 are strongly linked to allergy and asthma susceptibility.
 The Membrane Spanning (MS)4A gene cluster encodes a family of at least 16 genes in humans that are
expressed in immune cells. Current evidence suggests a link between the MS4A family and diseases associated
with inflammation. The entire MS4A gene cluster lies within 11q12-q13, suggesting a potential linkage to allergy.
In this application, we propose that the MS4A gene cluster plays a critical role in the development of a hyper-
responsive mast cell phenotype. Currently, only two of these genes have been studied in detail and both play
important roles in immune cell signaling and function. In this study, we will establish the roles of the MS4A gene
cluster in human mast cell function and identify MS4A proteins as novel regulators of FcεRI trafficking and
signaling that define human mast cell function and responsiveness to IgE signals in mast cells from non-diseased
and asthmatic lung. In addition to novel mechanisms that regulate mast cell function, these proteins could
represent new drug targets for asthma and other allergic diseases.

## Key facts

- **NIH application ID:** 10469692
- **Project number:** 5R01AI143985-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Glenn Paul Cruse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,978
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469692

## Citation

> US National Institutes of Health, RePORTER application 10469692, Regulation of FcεRI function by the MS4A gene cluster (5R01AI143985-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10469692. Licensed CC0.

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