# Autoimmune Diabetes: Macrophage Responses

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $471,535

## Abstract

ABSTRACT
The development of tissue-specific autoimmunity is a chronic process in which finely programmed autoimmune
responses progress and culminate in the target organ. Although the tissue environment is eventually dominated
by the invasive responses, regulatory elements that function to oppose such pathogenic activities remain
understudied. In type 1 diabetes (T1D), the insulin-producing β cells are targeted by self-reactive T cells
infiltrating into the pancreatic islets. Less appreciated is that before the entry of the first T cells, the islet
environment has established an intrinsic mechanism that restrains the onward autoimmune attack. Such
regulation is mediated by a specific subset of the islet resident macrophages specialized in the clearance of
apoptotic β cells, a process referred to as efferocytosis. The efferocytosis program induces anti-inflammatory
responses and when enhanced, imposes strong immunoinhibitory functions, leading to profound protection from
autoimmune diabetes. We hypothesize that the efferocytosis program may act as an original control mechanism
installed in the normal islet environment regardless of autoimmune propensity. This innate mechanism is
common in mice and humans and may considerably differ from other immunomodulatory elements (i.e.,
regulatory T cells (Tregs)), which are introduced along with the adaptive immune invasion. Therefore, examining
efferocytosis in islets will provide conceptual advances to the biological and autoimmune events taking place in
this important organ. Moreover, by analyzing the immunoinhibitory components associated with macrophage
efferocytosis, this project will provide translational and therapeutical insights relevant to human T1D. In this
proposal, we seek to thoroughly examine the efferocytic islet macrophages and define their role in regulating a
complex autoimmune process.

## Key facts

- **NIH application ID:** 10441877
- **Project number:** 1R01AI162591-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Xiaoxiao Wan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $471,535
- **Award type:** 1
- **Project period:** 2022-02-14 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441877

## Citation

> US National Institutes of Health, RePORTER application 10441877, Autoimmune Diabetes: Macrophage Responses (1R01AI162591-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10441877. Licensed CC0.

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