Project Details
Description
SUMMARY
This proposal aims to generate a Cre driver in mice that can be used to investigate the distinct functions and
contributions of type 3 innate lymphoid cells (ILC3s) in immune responses and diseases. ILC3s, similar to CD4+
helper T lymphocytes (Th), play crucial roles in host defense and in maintaining tissue homeostasis. However,
the functional overlap between ILC3s and Th17 cells has made it challenging to study their specific contributions
in these and other contexts. Our research team identified an ILC3-specific enhancer (E22-2) associated with the
Il22 gene, which encodes a type 3 signature cytokine. We now propose to generate a mouse strain with ILC3-
specific expression of GFP-IRES-Cre using CRISPR-mediated targeting of a single-copy BAC-Il22 reporter (22-
GFP) containing E22-2 and exhibiting GFP expression that is exquisitely restricted to mature ILC3s. The
specificity and extent of Cre-mediated deletion will be determined by crossing the ILC3-specific Cre mice (22-
GFPCre) with a flox-STOP-TdTomato reporter strain. Successful completion of this project will facilitate genetic
engineering and targeted manipulation to study the ILC3-specific functions of specific factors without
confounding effects on Th17 or iNKT17 cells. Examples of such future studies include establishing the roles of
type 3 cytokines (IL-22 and IL-17A/F) in controlling infections, inflammatory bowel diseases, oncogenesis, and
innate immune responses to cancer. Additionally, deployment of the new Cre driver will shed light on factors that
govern the functional plasticity of ILC3s in inflammatory settings.
Status | Active |
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Effective start/end date | 02/1/24 → 12/31/24 |
Funding
- National Institute of Allergy and Infectious Diseases: $70,875.00
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