Thursday, December 11, 2025 12/11/2025

The role of miR-142 in regulatory T cell Development and function

Award Number: R01AI146313
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/17/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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The role of miR-142 in regulatory T cell Development and function - Project Summary Regulatory T (Treg) cells are vital for maintaining immunological self-tolerance and restraining overreactive immune responses against infection. Aberrant Treg cell activity is associated with autoimmune diseases and unproductive immune responses against tumors. An insufficient understanding of the molecular mechanisms that govern Treg cell biology is one of the critical barriers hampering development of effective Treg cell-based therapies for autoimmunity and cancer. Post-transcriptional control of gene expression by microRNAs (miRNAs) has recently emerged as an essential genetic element for Treg cell differentiation and function. Thus, the objective of this proposal is to gain better understanding of how individual miRNAs control central aspects of Treg cell biology. Closing of this knowledge gap may allow us to develop novel, targeted immunotherapies for treatment of Treg cell-mediated diseases. The focus of this proposal is to elucidate the function of miR-142 in Treg cells. Our results using genetic knockout mouse models indicate that miR-142 is an indispensable regulator of Treg cell- mediated immunosuppression. We uncovered two distinct roles for miR-142 in Treg cells: it promotes thymic Treg cell differentiation and positively regulates mature Treg cell homeostasis and suppressive activity. Moreover, we mechanistically linked the impaired function of mature miR-142-deficient Treg cells with excessive IFNg production and signaling, and identified several IFNg-associated genes as direct molecular targets of miR-142. Thus, our overall hypothesis is that miR-142 plays a crucial role in thymic Treg cell development and controls Treg cell abundance and functional activity. Furthermore, we posit that miR-142 regulates mature Treg cell homeostasis and suppressive function by attenuating production of and responsiveness to IFNg. We will test our central hypothesis with three specific aims. In Aim 1, we will investigate the role of miR-142 in thymic Treg cell development and define its mode of action. In Aim 2, we will determine the impact of inducible miR-142 depletion on Treg cell homeostasis and suppressive function in the context of antitumor immune response. Finally, in Aim 3, we will identify the molecular mechanism of miR-142-mediated control of Treg cell activity. To that end, we will determine how dysregulated IFNg signaling impacts the immunosuppressive activity and homeostasis of miR-142-deficient Treg cells. The proposed research is significant because it is expected to advance our understanding of miRNA-mediated mechanisms underlying the control of Treg cell function and immune tolerance. Additionally, this study may potentially lay a foundation for developing a novel miR-142-based therapeutic strategy for modulating Treg cell activity in cancer immunotherapy and autoimmune disease settings.


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: 2026 ( Subtotal = $0 )
2026	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $440,000 )
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	8/16/2024	NON-COMPETING CONTINUATION	$440,000
														Subtotal = $440,000

Issue Date FY: 2023 ( Subtotal = $440,000 )
2023	2023	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	4	8/11/2023	NON-COMPETING CONTINUATION	$440,000
														Subtotal = $440,000

Issue Date FY: 2022 ( Subtotal = $440,000 )
2022	2022	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	3	8/15/2022	NON-COMPETING CONTINUATION	$440,000
														Subtotal = $440,000

Issue Date FY: 2021 ( Subtotal = $440,000 )
2021	2021	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	8/5/2021	NON-COMPETING CONTINUATION	$440,000
														Subtotal = $440,000

Issue Date FY: 2020 ( Subtotal = $440,000 )
2020	2020	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	9/16/2020	NEW	$440,000
														Subtotal = $440,000

Grand Total All Awards = $2,200,000

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The role of miR-142 in regulatory T cell Development and function

Award Number: R01AI146313

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/17/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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