# Gene transcription in SLE

> **NIH NIH R37** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $547,145

## Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder of largely unknown etiology characterized
by profound T cell effector dysfunction. SLE T cells produced reduced amounts of interleukin 2 (IL-2) which
contributes to the increased rate of infections, decreased generation of cytotoxic and regulatory T cells and
decreased ability to eliminate autoreactive T cells through activation-induced cell death. IL-2 production is
controlled at the transcription level by factors whose activity is influenced by membrane-initiated signaling
events. In parallel, T cells from patients with SLE produced increased amounts of the proinflammatory
cytokine IL-17. Studies in human SLE T cells which display increased levels of the transcriptional
repressor, cAMP responsive element modulator (CREM) and mice made to overexpress or lack CREM,
established that CREM is a transcriptional repressor for IL-2 and a transcriptional enhancer for IL-17. This
bidirectional effect is accomplished through epigenetic modifications of the IL-2 and IL-17 loci. A shorter
form of CREM, ICER, was found to be responsible for the increased production of IL-17 and to accomplish
this through distinct metabolic events. The studies will advance by generating ICER-specific deficient
mice and T cell-restricted ICER specific-deficient mice to study the role of ICER in the development of
autoimmunity and by determining the role of ICER/CREM in lymphocyte metabolism. The overall direction
will be to define the metabolic pathways that account for the apparent effector cell phenotype in
autoimmunity. In this way we will identify specific metabolic targets which will mitigate autoimmune
pathology.

## Key facts

- **NIH application ID:** 10085612
- **Project number:** 5R37AI049954-20
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** George C Tsokos
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $547,145
- **Award type:** 5
- **Project period:** 2001-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085612

## Citation

> US National Institutes of Health, RePORTER application 10085612, Gene transcription in SLE (5R37AI049954-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10085612. Licensed CC0.

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