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MHC class II presentation of Borrelia burgdorferi and synovial tissue antigens in murine Lyme arthritis

Award Number: R21AI148982
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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MHC class II presentation of Borrelia burgdorferi and synovial tissue antigens in murine Lyme arthritis - SUMMARY OF RESEARCH PROJECT Infections normally elicit an immune response that is sufficiently robust to enable pathogen killing, while also regulated to limit excessive inflammation and tissue damage. However, inappropriate regulation following infection may result in development of chronic inflammation and autoimmunity. This project will help determine how dysregulated T cell responses to specific Borrelia burgdorferi (Bb) and host antigens influence development of Lyme arthritis (LA) and Lyme-associated autoimmunity. Lyme disease, caused by infection with the tick-borne pathogen Bb, is usually effectively treated with antibiotic therapy. However, some patients may develop post-infectious disease manifestations following treatment with antibiotics, including post-infectious LA, which may cause long-term or permanent disability. Immune dysregulation and autoimmunity are possible contributing factors to post-treatment Lyme disease syndromes, which may last months or years after antibiotic therapy. In post-infectious LA, the inflamed synovial lesion is characterized by accumulation of inflammatory cellular infiltrate, autoreactive T and B cell responses, and marked synovial fibroblast proliferation, without any evidence of active infection. These features are similar to the histologic picture seen in other forms of chronic inflammatory arthritis, such as rheumatoid arthritis (RA), the prototypic autoimmune joint disease. The objective of this exploratory R21 proposal is to develop novel immunopeptidomics tools using animal models to identify candidate Bb and self-antigens and to study the biologically relevant antigen presenting cells that together are driving CD4+ T cell autoimmunity in LA. Once this work is complete, we will have established a tractable mouse model of Bb infection-induced autoimmunity, providing the research community resources necessary to rigorously study the foundational parameters of MHC-II induction of autoimmunity to specific self- antigens, which lie at the heart of pathogenesis in LA and other autoimmune diseases where infection is a suspected autoimmune trigger.


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 = -$3,817 )
2024	2021	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	2	11/15/2023	NON-COMPETING CONTINUATION	-$3,817
														Subtotal = -$3,817

Issue Date FY: 2021 ( Subtotal = $192,500 )
2021	2021	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	2	12/9/2020	NON-COMPETING CONTINUATION	$192,500
														Subtotal = $192,500

Issue Date FY: 2020 ( Subtotal = $231,000 )
2020	2020	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Allergy and Infectious Diseases Research	000	1	1/17/2020	NEW	$231,000
														Subtotal = $231,000

Grand Total All Awards = $419,683

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MHC class II presentation of Borrelia burgdorferi and synovial tissue antigens in murine Lyme arthritis

Award Number: R21AI148982

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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