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Skin derived pro-type 2 alarmins alter the gut antigen passage landscape and predispose to allergic gut tropism.

Award Number: F31AI200171
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Skin derived pro-type 2 alarmins alter the gut antigen passage landscape and predispose to allergic gut tropism. - Project Summary / Abstract Food allergies are a growing public health concern, with rising prevalence and severity in the western world. In the U.S., food allergy is reported to be present in nearly 7% of children (roughly 2 in every classroom) and 10% of adults. In 2013, the economic burden of childhood food allergy alone was estimated at $24.8 billion annually. Despite this impact, the standard of care remains strict food avoidance. A deeper understanding of the mechanisms that drive the progression from food antigen sensitization to clinical food allergy is urgently needed to enable development of novel targeted therapies. Early-life skin damage is a key risk factor for food allergy. Skin-damaging comorbidities like atopic dermatitis are associated with an increased risk of food sensitization and more severe allergic reactions. This has led to the concept that sensitization occurs through the skin. However, the mechanism by which skin sensitization leads to intestinal allergic inflammation and reactivity remains unclear. Notably, the route of antigen transport across the intestinal epithelium differs between tolerant and food allergic individuals. Goblet cell antigen passages (GAPs), deliver food antigen to lamina propria dendritic cells and are linked to oral tolerance. In food allergy, secretory antigen passages (SAPs) formed by goblet, Paneth, and enteroendocrine cells predominate. Preliminary data demonstrates that skin damage induces a shift toward a pro-allergic antigen passage landscape in the intestine. The current gap in knowledge is how early-life skin damage alters the antigen passage landscape and promotes allergic gut tropism and clinical reactivity. The central hypothesis of this proposal is that early-life skin damage drives a pro-allergic shift in the antigen passage landscape that predisposes the intestine to type 2 inflammation and clinical reactivity. To test this, two specific aims (SA) are proposed: SA1) Define the role of skin damage in the alteration of the antigen passage landscape. SA2) Define the role of an altered antigen passage landscape in the recruitment of a type 2 inflammation to the gut and the development of food anaphylaxis. The studies are anticipated to demonstrate the impact of skin-derived pro-type 2 alarmins in driving a pro-allergic antigen passage landscape and the importance of pro-allergic antigen passages in promoting allergic gut tropism and clinical reactivity. Successful completion of this work will 1) provide a novel and significant insight into the molecular mechanisms that drive the shift from sensitization through the skin to clinical reactivity to food antigens and identify skin damage derived alarmins as a major driver in pro-allergic antigen passage formation and promotion of allergic gut tropism and 2) provide Ms. Reichel with critical training in humanized animal models, computational analyses, advanced imaging techniques, scientific communication, and leadership.


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 = $44,162 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	001	1	5/19/2026	NEW	$0
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	1	5/19/2026	NEW	$44,162
														Subtotal = $44,162

Grand Total All Awards = $44,162

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Skin derived pro-type 2 alarmins alter the gut antigen passage landscape and predispose to allergic gut tropism.

Award Number: F31AI200171

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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