# Role of microbiota-TLR7/8 Interaction in systemic lupus erythematosus

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $699,657

## Abstract

PROJECT SUMMARY/ABSTRACT
Systemic lupus erythematosus (SLE) predominantly affects women, up to ten times more frequently than men,
and it occurs about five times more commonly in African Americans than in Caucasians. Although the primary
cause of SLE has not yet been identified, a combination of genetic, hormonal, and environmental factors is
known to contribute to the development of this disease. Studies during recent years suggest that the disease
process initiates in genetically susceptible subjects several years before the development of clinical disease and
it could be suppressed or accelerated by sex hormones and environmental factors including gut microbiota. This
suggests that increased understanding of the environmental and genetic factor interactions that
trigger/perpetuate the early events of disease processes and identification of early predictors of autoimmune
processes will help develop novel safe and effective strategies to control or prevent SLE, prior to the onset of
clinical disease. In this regard, using a pre-clinical model of lupus which shares the etiology and auto-antigen
epitopes with that of human SLE, we for the first time, demonstrate the contribution of pro-inflammatory events
and autoantibody production initiated in the gut mucosa at juvenile age, long before the onset of systemic
autoimmunity and clinical disease, in the onset of disease process. We have also identified a combination of
previously unknown molecular events that initiates gut-inflammation and autoantibody production in a TLR7/8-
gut microbiota interaction-dependent manner, and contributes to systemic autoimmunity and lupus disease
progression. Based on our preliminary observations, we hypothesize that “the systemic autoimmune process in
lupus is initiated and perpetuated by TLR7/8-gut microbiota interaction dependent inflammation and
autoantibody production in the gut mucosa, and inhibition of this interaction at pre-nephritis stages can effectively
prevent the disease in at-risk subjects, and suppress autoantibody production in lupus patients”. Here, we
propose studies: 1) to define the role of TLR7/8 -microbiota interaction dose in human SLE by associating gut
inflammation and permeability features with the expression levels of these receptors on immune cells, and
microbiota interaction-dependent pro-inflammatory responses of these cells, with autoimmunity and lupus
susceptibility; and 2) to elucidate the role of TLR7/8-gut microbiota interaction in initiating gut inflammation and
autoantibody production, and systemic autoimmunity using pre-clinical models. We will also determine the
potential of oral treatment with antagonists in preventing/suppressing gut inflammation, systemic autoimmunity
and disease incidence. Our proposed study will not only identify early pro-inflammatory events that initiate
systemic autoimmunity in lupus, but will also introduce the possibility of a novel and rational, oral therapy for
suppressing intestinal inflammation to ...

## Key facts

- **NIH application ID:** 10051383
- **Project number:** 5R01AI138511-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** CHENTHAMARAKSHAN VASU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $699,657
- **Award type:** 5
- **Project period:** 2018-11-06 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051383

## Citation

> US National Institutes of Health, RePORTER application 10051383, Role of microbiota-TLR7/8 Interaction in systemic lupus erythematosus (5R01AI138511-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051383. Licensed CC0.

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