# Role of IL-1alpha signaling in inflammatory diseases and host defense

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2022 · $390,951

## Abstract

ABSTRACT
Interleukin-1 (IL-1) family cytokines IL-1α and IL-1β, have emerged as principal mediators of multiple
inflammatory diseases. Both bind to the interleukin-1 receptor (IL-1R) to induce a proinflammatory signaling
cascade. Over the last decade, much progress has been made in defining the roles and regulation of IL-1β in
multiple disease models. Studies from our lab and others have highlighted the contributions of Nod-like
receptors (NLRs) and multi-protein complexes known as inflammasomes, and caspase-8 in the regulation of
IL-1β production and inflammation. In stark contrast to IL-1β, and despite being the first major human pyrogen
described, the regulation of IL-1α remains poorly understood. Notwithstanding the increasing appreciation of
the contribution of IL-1α in the pathogenesis of many important human diseases, the factors that control
functional IL-1α maturation remain completely obscure. Novel discoveries from our lab using a mouse model of
cutaneous inflammatory disease (Ptpn6spin mutant mice) suggest that the inflammatory disease progresses in
an inflammasome- and IL-1β-independent manner. Instead, inflammation in the Ptpn6spin model requires IL-
1α and is driven by receptor interacting protein kinase 1 (RIPK1). Except for these studies, our current
understanding of the roles and regulation of IL-1α in inflammatory disease is severely limited. The central goal
of this project is to identify the cellular and molecular mechanisms of IL-1α regulation and to provide critical
information essential for understanding the function of IL-1α.

## Key facts

- **NIH application ID:** 10462802
- **Project number:** 5R01AR056296-15
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Thirumala-Devi Kanneganti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,951
- **Award type:** 5
- **Project period:** 2008-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462802

## Citation

> US National Institutes of Health, RePORTER application 10462802, Role of IL-1alpha signaling in inflammatory diseases and host defense (5R01AR056296-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10462802. Licensed CC0.

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