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Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune Encephalomyelitis

Award Number: R01AI168063
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) and other autoimmune diseases constitute a major healthcare burden at a cost of >$125 billion per year. Autoimmune disorders arise from a failure of immunoregulatory networks. Regulatory T (Treg) cells expressing transcription factor forkhead box protein 3 (Foxp3) are indispensable components of these networks. Moreover, recent studies from several groups suggest that Treg cells also facilitate tissue repair, in addition to exerting immunosuppression. During autoimmune diseases, Treg cells are activated in lymphoid organs and home to non-lymphoid target tissues where they persist in specialized niches to limit inflammation and facilitate tissue repair. Our overall goal is to determine how these Treg cell niches operate in the central nervous system (CNS) to ameliorate autoimmune neuroinflammation at cellular and molecular levels. Direct visualization of cell behavior often leads to surprises, new hypotheses, and follow-up experiments contributing to a better understanding of the mammalian immune system, and how autoimmunity and infectious diseases can be effectively treated. Building on our expertise in two-photon (2-P) imaging at the cellular level, and Ca2+ signaling at the molecular level, we will use the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to: 1) elucidate the local cues that drive survival, functional organization in niches, and motility behaviors of Treg cells in the spinal cord; 2) investigate how Treg cells selectively target processes that incite neuroinflammation. Our experimental approach includes evaluation of the Piezo1 channels as promising therapeutic targets to selectively expand Treg cells, an ideal strategy to curb ongoing autoinflammatory responses while preserving the immune system’s ability to fight new infections. Although this proposal is targeted specifically to MS, in a broader context our project will provide fundamental insights into how Treg cells fine-tune tissue inflammation so that better Treg-modifying therapies can be developed for autoimmune disorders, organ transplantation, cancer, and infectious diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $454,494 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Allergy and Infectious Diseases Research	000	3	1/31/2024	NON-COMPETING CONTINUATION	$454,494
														Subtotal = $454,494

Issue Date FY: 2023 ( Subtotal = $496,903 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Allergy and Infectious Diseases Research	000	2	2/6/2023	NON-COMPETING CONTINUATION	$496,903
														Subtotal = $496,903

Issue Date FY: 2022 ( Subtotal = $496,903 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Allergy and Infectious Diseases Research	000	1	3/1/2022	NEW	$496,903
														Subtotal = $496,903

Grand Total All Awards = $1,448,300

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Tissue-Specific Mechanisms of Regulatory T Cells in the CNS during Autoimmune Encephalomyelitis

Award Number: R01AI168063

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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