# Functions of CD177 as a novel IgG Fc receptor

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2020 · $231,000

## Abstract

PROJECT SUMMARY
Antibody therapy becomes indispensable for the treatment of infection, cancer, and inflammatory disease.
Nevertheless, clinical responses to antibody therapy vary markedly and efficacies of antibody therapy are
largely unpredictable in patients. To date, the genetic factors affecting the efficacy of antibody therapy remain
incompletely understood. Almost all successful therapeutic antibodies are IgGs, which require IgG Fc receptors
(or FcγRs) on immune cells to elicit effective immune functions. FcγRs are essential links between target cells
opsonized by therapeutic antibodies and effector immune cells that are responsible for killing the infected and
abnormal cells in immunotherapy. Humans use a number of FcγRs to mediate distinctive immune cellular
functions and functional FcγR genetic variants significantly impact immune responses. In preliminary studies,
we found that human CD177 specifically binds IgG but to IgA, suggesting that CD177 is an IgG Fc receptor.
CD177 is selectively expressed in bone marrow cells and has a role in the proliferation and differentiation of
myeloid lineage cells including neutrophils, myelocytes, promyelocytes, megakaryocytes, and early
erythroblasts. CD177 is exclusive expressed on neutrophils among circulating leukocytes with the percentages
of CD177+ neutrophils ranging from 0% to 100% in individuals. Notably, CD177 deficiency is a common
phenotype as 3–5% human populations completely lack CD177 expression. Our group was the first to
delineate genetic mechanisms of CD177 deficiency and expression variations. CD177 is able to mediate
neutrophil activation, but the physiological ligands and immune functions of CD177 remain poorly understood.
We hypothesize that CD177 is a novel IgG Fc receptor and that the CD177 genetic variants significantly
affect IgG-mediated immune functions. The rationale/premise of the proposed study is that the definition of
CD177 as novel functional IgG Fc-receptor will fill the critical knowledge gap about the full repertoire of human
FcγRs, which are essential for antibody-mediated responses. We will test our hypothesis by pursuing the
following Specific Aims: 1) to test the hypothesis that CD177 is a novel IgG Fc receptor (FcγR); 2) to test the
hypothesis that CD177 genetic variants affect the interaction between human IgG and CD177; and 3) to test
the hypothesis that CD177 affects IgG-mediated immune functions. Our study will provide novel insights into
CD177-mediated immune functions and into the genetic mechanisms underlying response variability of
antibody therapy. CD177 may serve as valuable biomarkers in antibody therapy and vaccinations.

## Key facts

- **NIH application ID:** 9873699
- **Project number:** 1R21AI149395-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JIANMING WU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-02-21 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873699

## Citation

> US National Institutes of Health, RePORTER application 9873699, Functions of CD177 as a novel IgG Fc receptor (1R21AI149395-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873699. Licensed CC0.

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