# TLR Transporters in Lupus

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $387,000

## Abstract

PROJECT SUMMARY
Nucleic acid-sensing (NA)-TLRs, particularly the TLR7 and TLR9, play a fundamental role in the development
of lupus and deletion or inhibition of NA-TLR signaling has been shown to have therapeutic efficacy. Recent
studies have elucidated the mechanism by which NA-TLRs traffick from the endoplasmic reticulum to the
endolysosomal compartment where they provide signals to activate cells and the immune system. This project
will investigate the role of endosomal transporters that appear to be necessary for NA-TLR signaling. These
endosomal complex are part of a intracellular trafficking system required for the biogenesis and function of
lysosome-related organelles. Deficiency of these complexes are linked to a rare recessive disorder,
Hermansky-Pudlak syndrome. This project will study the role HPS genes in TLR signaling and autoimmunity
looking specifically at AP-3, BLOC-1 to-3. This will be accomplished by defining the role of these gene in the
development of lupus (aim1), defining the role of AP-3 in TLR signaling in B cells (aim 2), and defining how
these four genes function in TLR transport and signaling (aim 3). By accomplishing these aims, this project will
provide a comprehensive view of the role of LRO biogenesis in endosomal TLR signaling of autoantibody-
relevant immune cells and in the development of lupus, by studying the whole animal, immune function, and at
the cellular levels. These studies are relevant to SLE and will provide an increased understanding of the
disease pathogenesis with the possibility of applying this information to the bedside.

## Key facts

- **NIH application ID:** 10217974
- **Project number:** 5R01AI136492-04
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DWIGHT H KONO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,000
- **Award type:** 5
- **Project period:** 2018-08-28 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217974

## Citation

> US National Institutes of Health, RePORTER application 10217974, TLR Transporters in Lupus (5R01AI136492-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217974. Licensed CC0.

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