Monday, February 16, 2026 2/16/2026

Role of Macrophage in Osteoimmunology with Aging

Award Number: R01AG076731
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Role of Macrophage in Osteoimmunology with Aging - Project Summary/Abstract T helper cells (Th1 and Th17) play an important role in bone homeostasis through regulating osteoclast (OC) formation in autoimmune diseases and OVX-induced osteoporosis. However, how these T cells interactions with bone cells disrupt bone homeostasis during aging to cause bone loss in age-related osteoporosis (AROP) remains poorly understood. We reported that TGFβ1 (Tβ1) is a major bone loss-causing cytokine in AROP. It induces lysosomal degradation of TRAF3, a receptor adaptor protein that negatively regulates NF-κB activation, in mesenchymal progenitor cells (MPCs) to directly inhibit bone formation. However, the release of active Tβ1 from resorbing bone is limited because of low bone turnover in AROP. We have identified a novel subset of CD11b+F4/80+Ly6ChiLy6G- macrophages expressing membrane-bound Tβ1 (mbTβ1), which we call MbTβ1Macs, whose numbers are increased in the bone marrow (BM) of aged mice. MbTβ1Macs also express ITGB8 which can directly activate mTβ1. MbTβ1Macs have less potential to form OCs, but significantly inhibit osteoblast (OB) differentiation. Th1 cells expressing IFN-γ and senescent/immune checkpoint PD-1 are also increased in the BM of aged mice. IFN-γ induces Ly6Chi macrophages to express mbTβ1, which in turn stimulates Th1 cells producing IFN-γ and PD-1 in vitro, associated with reduced levels of TRAF3. These effects are blocked by the FDA approved lysosomal inhibitor, hydroxychloroquine (HCQ). Our proposed studies will 1) determine if ITGB8 activates mbTβ1 in MbTβ1Macs to inhibit bone formation during aging; 2) determine if IFN- γ polarizes MbTβ1Macs, which in turn promote Th1 cell senescence with enhanced production of inflammatory factors via Tβ1 induction of TRAF3 lysosomal degradation in aged mice; and 3) evaluate if our recently patented bone-targeted HCQ, with dual anti-resorptive and anabolic effects in an OVX-induced osteoporotic model, can prevent and treat AROP and low level chronic inflammation during age by blocking the reciprocal interactions between macrophages and Th1 cells. Completion of the proposed studies will identify novel mechanisms to explain the disruption of bone homeostasis during aging through reciprocal interactions between macrophages and Th1 cells, in which this novel subset of macrophages inhibits bone formation and causes BM low-level chronic inflammation by stimulating Th1 cells to produce inflammatory factors. Importantly, it will provide proof of principle that a bone-targeted HCQ may be a novel treatment for AROP.


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 = $373,530 )
2026	2026	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	000	5	1/21/2026	NON-COMPETING CONTINUATION	$373,530
														Subtotal = $373,530

Issue Date FY: 2025 ( Subtotal = $406,731 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	000	4	1/17/2025	NON-COMPETING CONTINUATION	$373,530
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	001	4	8/11/2025	NON-COMPETING CONTINUATION	$33,201
														Subtotal = $406,731

Issue Date FY: 2024 ( Subtotal = $415,033 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	001	3	6/10/2024	NON-COMPETING CONTINUATION	$41,503
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Aging Research	000	3	2/2/2024	NON-COMPETING CONTINUATION	$373,530
														Subtotal = $415,033

Issue Date FY: 2023 ( Subtotal = $441,855 )
2023	2023	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Aging Research	000	2	2/10/2023	NON-COMPETING CONTINUATION	$441,855
														Subtotal = $441,855

Issue Date FY: 2022 ( Subtotal = $441,855 )
2022	2022	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Aging Research	000	1	4/21/2022	NEW	$441,855
														Subtotal = $441,855

Grand Total All Awards = $2,079,004

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Macrophage in Osteoimmunology with Aging

Award Number: R01AG076731

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer