# Molecular Regulation of B cells and T cells in Human SLE

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $1,124,031

## Abstract

The overarching objective of the Emory Autoimmunity Center of Excellence (ACE) U19 is to
decipher the molecular programs responsible for the aberrant effector immune responses that
lead to autoimmune disease. Specifically, based on the work performed by the Emory ACE
during the current funding cycle, we postulate that epigenetic regulation of effector B cell
differentiation and function is a critical pathogenic component of Systemic Lupus
Erythematosus (SLE). Further, we contend that disease-related epigenetic imprinting is first
established at early stages of B cell development and then maintained throughout the
differentiation of naïve cells into their effector progeny upon activation by antigens and co-
stimulatory pathways. Finally, we propose that SLE will also be characterized by abnormal
regulation of other critical effector immune responses, namely CD8 T cells and in particular,
the stem-like population responsible for the maintenance of antigen-specific responses in
chronic viral infections and anti-tumor responses in patients treated with checkpoint inhibitors.
The fundamental goals of the Emory ACE are: 1) to understand B cells and CD8 T cells
dysregulation in human SLE; and 2) to assemble a scientific and technological platform that
engages other ACE U19 and UM1 Centers to perform similar studies in other immune cells
and autoimmune disorders. The specific aims of the Emory ACE U19 are: Aim 1: To establish
an Administrative Core (I. Sanz, Core Director) for the successful operation of the ACE U19
Scientific Program and its interaction with the ACE Network; Aim 2: To develop a highly
integrated Emory ACE U19 Scientific Program comprised of the following components:
Principal Project (Sanz, PI): Mechanisms of B cell dysregulation in human SLE; Collaborative
Project (Boss, PI): Epigenetic regulation of autoimmune responses; Pilot Project (Ahmed, PI):
Characterization of stem-like CD8 T cells in SLE. The expected results will unravel disease
pathogenesis; segment patients; design personalized therapies; and develop biomarkers of
disease onset, evolution, and outcome. Our efforts will naturally dovetail with the mission of the
UM1 ACEs centers and contribute greatly to the charter mission of the ACE network.

## Key facts

- **NIH application ID:** 10240986
- **Project number:** 3U19AI110483-07S2
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Ignacio E. Sanz
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,124,031
- **Award type:** 3
- **Project period:** 2020-08-26 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240986

## Citation

> US National Institutes of Health, RePORTER application 10240986, Molecular Regulation of B cells and T cells in Human SLE (3U19AI110483-07S2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240986. Licensed CC0.

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