Thursday, December 26, 2024 12/26/2024

The IL-23/IL-17 Axis in Inflammatory Arthritis

Award Number: R01AR062173
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract About 50 million Americans (22%) suffer from some form of inflammatory arthritis and estimates are that, with the aging population worldwide, 67 million adults will have arthritis by 2030 with an economic impact higher than $128 billion dollars. Although interleukin-23 (IL-23) has been implicated in the pathogenesis of arthritis, the molecular mechanisms remain unknown. Since the discovery of IL-23 regulation of pathogenic T helper cells that express interleukin-17 (Th17) the importance of direct actions of IL-23 in arthritis is overshadowed. To highlight its importance we developed gene-transfer models of IL-23 and IL-17A and using these models we established that IL-23 is a potent inducer of arthritis, independently of IL-17A. Dissection of IL-23 from the IL- 23/IL-17A axis has allowed us to uncover novel mechanisms of myeloid cell activation previously overlooked. We identified that IL-23 induces arthritis independently of Th17 cells and through activation of myeloid cells. T cells and myeloid cells share a requirement for costimulatory signals that are mediated by ITAMs. The ITAM is a conserved signalling motif contained in the cytoplasmic domain of transmembrane adaptor molecules that are associated and transmit signals from various immunoreceptors present in haematopoietic progenitors. We have identified that IL-23 induces the activation and recruitment of MDL-1 receptor that orchestrates synovial and skin inflammation via the activation of osteoclasts and neutrophils respectively. Discovering the cellular and molecular mechanisms that dictate recruitment and activation of osteoclasts in inflammatory arthritis is central to preventing this disabling condition. Detailed understanding of these cellular and molecular interactions will yield insights into regulation of arthritis that can be exploited for therapeutic interventions.


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: 2025 ( Subtotal = $543,762 )
2025	2025	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	11/27/2024	NON-COMPETING CONTINUATION	$543,762
														Subtotal = $543,762

Issue Date FY: 2024 ( Subtotal = $735,191 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	12/12/2023	NON-COMPETING CONTINUATION	$748,547
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	9	5/17/2024	NON-COMPETING CONTINUATION	-$13,356
														Subtotal = $735,191

Issue Date FY: 2023 ( Subtotal = $245,949 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	8	9/11/2023	SUPPLEMENT FOR EXPANSION	$245,949
2023	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	11/30/2022	SUPPLEMENT FOR EXPANSION	$0
2023	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	8	12/1/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $245,949

Issue Date FY: 2022 ( Subtotal = $601,333 )
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	8	11/24/2021	NON-COMPETING CONTINUATION	$479,346
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	8	11/29/2021	SUPPLEMENT FOR EXPANSION	$71,575
2022	2022	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	009	8	8/5/2022	NON-COMPETING CONTINUATION	$47,932
2022	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	6	2/8/2022	NON-COMPETING CONTINUATION	-$17,734
2022	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	008	6	2/8/2022	SUPPLEMENT FOR EXPANSION	-$18,033
2022	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	10/28/2021	SUPPLEMENT FOR EXPANSION	-$48,125
2022	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	10/28/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$50,605
2022	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	007	7	2/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$348,726
2022	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	5	2/8/2022	COMPETING CONTINUATION	-$290,907
2022	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	006	5	2/8/2022	SUPPLEMENT FOR EXPANSION	-$22,052
														Subtotal = $601,333

Issue Date FY: 2021 ( Subtotal = $577,348 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	6	7/13/2021	NON-COMPETING CONTINUATION	-$66,158
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	6	7/14/2021	SUPPLEMENT FOR EXPANSION	$66,158
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	11/23/2020	NON-COMPETING CONTINUATION	$494,806
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	6	8/2/2021	NON-COMPETING CONTINUATION	-$451,384
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	7	8/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$493,456
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	4/20/2021	NON-COMPETING CONTINUATION	$40,470
														Subtotal = $577,348

Issue Date FY: 2020 ( Subtotal = $505,680 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	8/10/2020	SUPPLEMENT FOR EXPANSION	$22,052
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	12/27/2019	COMPETING CONTINUATION	$483,628
														Subtotal = $505,680

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2015	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	5/23/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/7/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $471,839 )
2015	2015	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/17/2015	NON-COMPETING CONTINUATION	$471,839
														Subtotal = $471,839

Issue Date FY: 2014 ( Subtotal = $462,402 )
2014	2014	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	3/18/2014	NON-COMPETING CONTINUATION	$462,402
														Subtotal = $462,402

Issue Date FY: 2013 ( Subtotal = $388,634 )
2013	2013	UNIVERSITY OF CALIFORNIA	1441 RESEARCH PARK DRIVE	DAVIS	CA	95616	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	9/17/2013	SUPPLEMENT FOR EXPANSION	$59,459
2013	2013	UNIVERSITY OF CALIFORNIA	1441 RESEARCH PARK DRIVE	DAVIS	CA	95616	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	4/11/2013	NON-COMPETING CONTINUATION	$311,850
2013	2013	UNIVERSITY OF CALIFORNIA	1441 RESEARCH PARK DRIVE	DAVIS	CA	95616	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	7/15/2013	NON-COMPETING CONTINUATION	$17,325
														Subtotal = $388,634

Issue Date FY: 2012 ( Subtotal = $333,185 )
2012	2012	UNIVERSITY OF CALIFORNIA	1441 RESEARCH PARK DRIVE	DAVIS	CA	95616	YOLO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	3/23/2012	NEW	$333,185
														Subtotal = $333,185

Grand Total All Awards = $4,865,323

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The IL-23/IL-17 Axis in Inflammatory Arthritis

Award Number: R01AR062173

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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