# Development and function of innate-like gamma delta T cells

> **NIH NIH R21** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $234,000

## Abstract

Project Summary:
 Innate-like γδ T cells are unusual T cells that are highly enriched in mucosal tissues like the lung, gut,
and skin, where they play critical roles in the host immune response to pathogens, in autoimmunity, in anti-
tumor immunity, and in tissue repair/homeostasis. A defining characteristic of innate-like γδ T cells is their ability
to rapidly produce large amounts of cytokines (e.g., IFN-γ, IL-4, and IL-17), chemokines, and growth factors
which allows them to shape both the magnitude and quality of both the developing immune response. Although
a large fraction of γδ T cells exhibit innate-like T cell characteristics, evidence in both mouse and humans
indicates the presence of naïve, unpolarized γδ T cells. The mechanisms/pathways that confer an innate-like
phenotype on developing γδ T cells remain largely undefined. Both our recently published and preliminary data
indicate that the SLAM/SAP signaling pathway is intimately involved in the development and function of innate-
like γδT cells, and that it works through multiple distinct pathways. Here, w e p r o p o s e t o use a single-cell
multiomics approach that includes scCITEseq coupled with a customized γδ V(D)J profiling platform and
scATACseq to define the gene regulatory programs that distinguish SAP-dependent innate-like γδ T cells during
development. Our preliminary data suggest that the SLAM/SAP signaling pathway functions at a very early stage
of γδ T cell development, is involved in shaping the γδ TCR repertoire, and reveals the presence of SAP-
dependent γδ TCR clonotypes. Altogether, these published and unpublished lead us to hypothesize that
SLAM/SAP signaling regulates the development of functionally distinct innate-like γδ TCR clonotypes. To test
this hypothesis, we will i) define the gene regulatory programs that distinguish SAP-dependent and SAP-
independent thymic γδ T cells during development and ii) define the mechanisms through which SLAM/SAP
signaling regulates innate-like γδ T cell developmental and function. Upon completion of these Aims, we expect
to have defined new SAP-dependent innate-like γδ T cell subsets and to have generated a comprehensive map
of the SAP-dependent gene regulatory programs of γδ T cells at different stages of development. In addition,
we will have made a significant step forward in defining one of the mechanisms that regulates innate-like γδ T
cell development and function. We believe this information will be a critical step forward in defining the
developmental requirements that define these lineages as well as their specific contributions to the immune
response.

## Key facts

- **NIH application ID:** 10527432
- **Project number:** 1R21AI166465-01A1
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** JONATHAN E BOYSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2022-05-18 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527432

## Citation

> US National Institutes of Health, RePORTER application 10527432, Development and function of innate-like gamma delta T cells (1R21AI166465-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10527432. Licensed CC0.

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