# The Role of Dendritic Cells in Regulating the Gut-Brain Immune Axis in Ischemic Stroke

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $441,487

## Abstract

Project Summary/Abstract
Stroke is a prevalent and devastating disease with limited therapeutic options. Inflammation and
immune cells are major components in the pathophysiology of ischemic stroke and contribute to acute
and delayed tissue injury. However, our incomplete understanding of the factors regulating the immune
responses triggered by cerebral ischemia remains a significant obstacle to the development of effective
therapeutic interventions based on modulating post-ischemic inflammation. Besides activation of brain
resident immune cells, ischemic stroke is characterized by the recruitment of peripheral innate and
adaptive immune cells that participate in the inflammatory response and contribute to the damage.
Commensal microbiota that populate epithelial surfaces play a defining role in shaping the immune
system, the development, maintenance and function of which depends critically on the relative
abundance and composition of the different microbial species. In particular, intestinal commensal
bacteria, the most abundant symbiotic compartment in the body, have emerged as a potent regulator of
the immune response to stroke. The long-term goal of this research program is to elucidate the role of
intestinal microbiota in stroke pathobiology and develop the experimental framework for new
preventative and therapeutic approaches for ischemic stroke. In the present application, we will test the
hypothesis that the interaction of commensal intestinal microbiota with dendritic cells is a critical
determinant of stroke outcome by modulating the immune system and inflammatory response to
cerebral ischemia. Supported by relevant preliminary results, this application will test the hypothesis
that commensal intestinal microbiota modulate stroke outcome by acting on intestinal dendritic cells to
either induce a tolerogenic or pro-inflammatory phenotype affecting T cell differentiation. These
intestinal immune changes propagate to the brain and meninges after stroke by increased immune cell
trafficking. To this end, we will determine (a) the roles of different dendritic cell populations in mediating
the neuroprotective effects of altered microbiota and (b) the cellular and molecular targets of microbiota
that lead to altered intestinal immunity and their importance for stroke outcome. These goals will be
achieved using a mouse model of transient focal cerebral ischemia with assessment of histological and
neurological outcome, a model of altered gut bacteria, cell tracking of intestinal immune cell, and in vitro
immune cell coculture models. This proposal may open the way to new avenues for stroke prevention
and therapy based on modulation of the immune system by the gut microbiota.

## Key facts

- **NIH application ID:** 10797010
- **Project number:** 5R01NS132493-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Josef Anrather
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,487
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797010

## Citation

> US National Institutes of Health, RePORTER application 10797010, The Role of Dendritic Cells in Regulating the Gut-Brain Immune Axis in Ischemic Stroke (5R01NS132493-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10797010. Licensed CC0.

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