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Investigation of AhR Ligands on FcGamma Receptor Signaling: Consequences of Antibody Suppression

Award Number: R15ES027650
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Investigation of AhR Ligands on FcGamma Receptor Signaling: Consequences of Antibody Suppression - ABSTRACT: It is well known that TCDD and other aryl hydrocarbon receptor (AhR) ligands suppress antibody production but there is little information about the consequences of decreased antibody production on signaling through Fcg receptors (FcgR). FcgRs are expressed on several cell types and upon being bound by IgG antibodies (and their subtypes, such as IgG1 or IgG3), initiate various effector functions including opsonization, neutralization, agglutination, complement activation, and activation of antibody-dependent cell-mediated cytotoxicity (ADCC). Thus, IgG and its subtypes play critical roles in the immune response to pathogens and in autoimmune diseases. Since TCDD and other AhR ligands have been shown to suppress IgG antibody levels, there is potential for AhR ligands to attenuate IgG-mediated effector function. Thus, the overall goal of this R15 is to connect the relatively well-characterized effects of AhR ligands on IgG antibody production with the understudied effects of AhR ligands on signaling on target cells bearing FcgR. We will test the hypothesis that AhR ligand-induced suppression of IgG antibody production leads to suppression of antibody-dependent immune responses. The hypothesis will be tested with three specific aims (SAs). SA1 is to characterize the mechanisms by which AhR ligands suppress human IgG antibody production. SA2 is to evaluate the direct effect of AhR ligands on FcgR-stimulated cells. SA3 is to evaluate the effect of AhR ligand-treated B cells to stimulate FcgR- expressing cells. Results from these studies will provide important information on the mechanism by which TCDD is immunotoxic and might also identify other non-toxic AhR ligands that have the potential to be effective therapies for autoimmune 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: 2025 ( Subtotal = $0 )
2025	2022	MISSISSIPPI STATE UNIVERSITY	245 BARR AVE	MISSISSIPPI STATE	MS	39762	OKTIBBEHA	USA	Environmental Health	000	2	7/17/2025	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $419,864 )
2022	2022	MISSISSIPPI STATE UNIVERSITY	245 BARR AVE MCARTHUR HALL	MISSISSIPPI STATE	MS	39762	OKTIBBEHA	USA	Environmental Health	001	2	8/3/2022	COMPETING CONTINUATION	$419,864
2022	2017	MISSISSIPPI STATE UNIVERSITY	245 BARR AVE MCARTHUR HALL	MISSISSIPPI STATE	MS	39762	OKTIBBEHA	USA	Environmental Health	000	1	2/14/2022	NEW	$0
														Subtotal = $419,864

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	MISSISSIPPI STATE UNIVERSITY	245 BARR AVE MCARTHUR HALL	MISSISSIPPI STATE	MS	39762	OKTIBBEHA	USA	Environmental Health	000	1	8/31/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $436,500 )
2017	2017	MISSISSIPPI STATE UNIVERSITY	245 BARR AVE MCARTHUR HALL	MISSISSIPPI STATE	MS	39762	OKTIBBEHA	USA	Environmental Health	000	1	9/14/2017	NEW	$436,500
														Subtotal = $436,500

Grand Total All Awards = $856,364

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Investigation of AhR Ligands on FcGamma Receptor Signaling: Consequences of Antibody Suppression

Award Number: R15ES027650

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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