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

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $521,026

## Abstract

Project Summary/Abstract
 Generation of adaptive immune responses to vaccines and infections necessitates highly coordinated
crosstalk between cells of the innate and adaptive immune system. Using advanced imaging approaches, which
we developed, we have recently established that lymph nodes are organized into discrete micro-environments
(MEs) composed of different innate immune cell populations. In the past award cycle, we developed additional
3D quantitative imaging tools and described novel features of innate cell organization in lymph nodes. Moreover,
we used these approaches to study how innate cell MEs change during distinct types of inflammation (Type-I
vs. Type-II), and which MEs are associated with distinct types of T cell effector programming. We found that the
generation of highly divergent innate MEs is involved in programing of Type-I vs. Type-II T cell responses. We
also demonstrated that activation of T cells within distinct innate MEs leads to very rapid early heterogeneity in
the developing adaptive immune response. These findings raise the central hypothesis of the current follow-up
proposal, that lymphoid tissues are composed of a mosaic of innate MEs, which dynamically respond to
specific inflammatory stimuli, and which are directly involved in the generation of distinct programs of
T cell immunity. The Objectives and corresponding Specific Aims of this renewal proposal are: 1) to continue
characterizing the cellular and molecular signaling events involved in the generation of innate cell MEs during
Type-I inflammation; 2) to elucidate the roles of lymphatic drainage mediated antigen and agonist dispersal
across lymphoid tissues in the establishment of diverse innate MEs and the generation of downstream adaptive
response heterogeneity, and 3) to determine the impact of paracrine cell-cell signaling in driving the formation of
Type-II MEs and Th2 cell differentiation (Aim 3). Our rationale is that a better understanding of how lymphoid
tissue microanatomy impacts innate and adaptive cell crosstalk during distinct types of inflammation, will help
reveal the underlying principles of immune response generation to vaccines and infections. A long-term goal of
our studies is to use this information to develop novel approaches to manipulate immune responses directly in
vivo. This would have major ramifications and clinical significance in improving human health.

## Key facts

- **NIH application ID:** 10791738
- **Project number:** 5R01AI134713-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Michael Gerner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $521,026
- **Award type:** 5
- **Project period:** 2018-02-17 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791738

## Citation

> US National Institutes of Health, RePORTER application 10791738, The Roles of Lymphoid Tissue Microenvironments in Guiding the Immune Response (5R01AI134713-07). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10791738. Licensed CC0.

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