Saturday, May 18, 2024 5/18/2024

Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells

Award Number: R01AI127726
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Project Summary Consistent with its functions in maintaining barrier integrity and preventing infection, the skin is home to a number of specialized T cell populations that not only combat infection but also work in concert to help maintain normal tissue homeostasis and promote wound repair. However, despite significant advances in understanding cutaneous immunity, the specific functions of different populations of cutaneous T cells, their roles in maintaining normal skin homeostasis, and contributions to inflammatory diseases of the skin remain poorly understood. In this respect, reliance on animal models can be problematic due to fundamental structural differences in the skin in humans vs. mice, and a lack of direct correspondence between cutaneous T cell populations in these species. Additionally, although skin-tropic T cells can be readily identified in peripheral blood based on their expression of the cutaneous lymphocyte antigen (CLA), the developmental and functional relationship of these cells in the blood with the different populations of T cells in the skin is still poorly understood. We have identified a novel population of CLA+CD4+ T cells in the peripheral blood of healthy subjects that expresses the CD103 integrin and produces the novel cytokine combination of IL-22, GM-CSF and IL-13 upon activation (CD103+CLAhi cells). Interestingly, this cytokine combination is also produced by phenotypically similar epidermal CD103 CLA CD69 TRM in the skin itself. Based on the ability of IL-22 to promote + hi + keratinocyte proliferation, migration and production of antimicrobial peptides, and GM-CSF and IL-13 to act on fibroblasts, and to mediate the differentiation of monocytes and macrophages into `alternatively activated' cells that promote tissue repair, we hypothesize CD103+CLAhi T cells in the blood represent a recirculating fraction of CD103+CLAhi TRM, and that these cells help coordinate the host-protective and wound healing responses following tissue damage in the skin. As such, these cells have the potential to be manipulated therapeutically to promote sterile wound healing and to optimize the development and function of engineered tissue grafts. In this proposal, we will use in vitro analyses and innovative humanized mouse models to test these hypotheses, assessing the developmental origins and trafficking behavior of CD103+CLAhi cells and determining their function during cutaneous tissue-repair responses.


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 = $0 )
2024	2021	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	5	10/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $485,684 )
2021	2021	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	5	5/13/2021	NON-COMPETING CONTINUATION	$485,684
														Subtotal = $485,684

Issue Date FY: 2020 ( Subtotal = $485,684 )
2020	2020	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	4	5/29/2020	NON-COMPETING CONTINUATION	$485,684
														Subtotal = $485,684

Issue Date FY: 2019 ( Subtotal = $851,247 )
2019	2019	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	001	3	7/11/2019	NON-COMPETING CONTINUATION	$365,563
2019	2019	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	3	5/6/2019	NON-COMPETING CONTINUATION	$485,684
														Subtotal = $851,247

Issue Date FY: 2018 ( Subtotal = $485,684 )
2018	2018	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	2	5/7/2018	NON-COMPETING CONTINUATION	$485,684
														Subtotal = $485,684

Issue Date FY: 2017 ( Subtotal = $503,184 )
2017	2017	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	1	6/20/2017	NEW	$503,184
														Subtotal = $503,184

Grand Total All Awards = $2,811,483

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells

Award Number: R01AI127726

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer