# The Roles of Lymphoid Tissue Microenvironments in Guiding the Immune Response

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $441,250

## Abstract

The innate and adaptive arms of the immune system are integrally linked, with dendritic cells (DCs), innate
antigen presenting cells, providing critical instructions to elicit the generation of adaptive T cell immunity. Using
a novel analytical imaging approach, we recently uncovered that different DC populations are asymmetrically
distributed in steady-state mouse lymph nodes, creating highly segregated zones composed of one or another
DC subset. Given that these DC populations have well-characterized differences in their abilities to elicit distinct
types of T cell responses, these findings raise the central hypothesis of this proposal, that lymphoid tissues
are composed of a mosaic of previously unappreciated DC microenvironments that are uniquely
dedicated for the generation of specific programs of T cell immunity. The objective of this grant is to
characterize these innate cell microenvironments during the steady-state and inflammation in both mice and
humans, and to study how they influence adaptive immune responses to vaccines. We will accomplish this goal
in three Specific Aims. In Aim 1, we will perform a comprehensive characterization of DC microenvironments in
mouse and human lymph nodes during the steady-state and after induction of inflammation with distinct vaccine
adjuvants. In Aim 2, we will investigate the molecular mechanisms regulating DC positioning in lymphoid tissues.
In Aim 3, we will interrogate how the spatial organization of DCs influences CD4+ and CD8+ T cell responses
to vaccines. Our rationale is that a better understanding of lymphoid tissue microanatomy, with respect to innate
and adaptive immune cell crosstalk, will help reveal the underlying principles of immune response generation
to vaccines. A long-term goal of our studies is to develop novel approaches to manipulate in vivo cellular
positioning in order to better modulate and fine-tune the innate and adaptive response to vaccines. In summary,
the proposed studies are significant, as they will advance our basic understanding of how immune responses
are generated in vivo, while also promoting development of novel strategies for immunomodulatory therapeutics
and vaccines.

## Key facts

- **NIH application ID:** 10088376
- **Project number:** 5R01AI134713-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Michael Gerner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,250
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088376

## Citation

> US National Institutes of Health, RePORTER application 10088376, The Roles of Lymphoid Tissue Microenvironments in Guiding the Immune Response (5R01AI134713-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10088376. Licensed CC0.

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