This project builds on our novel finding that topically applied engineered nanomaterials (ENMs) can modulate allergic immune responses in skin. Using a contact hypersensitivity (CHS) mouse model we discovered that some ENMs suppress skin inflammation which is therapeutically relevant and others exacerbate allergic symptoms suggesting an increased hazard for cutaneous ENM exposure particularly for individuals whom suffer with allergic contact dermatitis (ACD). In fact, 15-20% of the US population is diagnosed with ACD which accounts for 95% of reported occupational skin disease and is the third most common reason patients visit a dermatologist. With the expanding industrial and consumer use of ENMs there is a growing risk that individuals with ACD may simultaneously come into skin contact with environmental allergens or chemical sensitizers and ENMs through use of nano- enabled products or from occupational exposures. The primary goal of this project is to understand the cellular and molecular mechanisms of how ENMs modulate allergic skin immune responses for which little is currently understood. We have defined an early time window of action within which ENMs exert their effects and our data suggests an important connection with mast cells (MCs). The central hypothesis of this project is that ENMs exert immunomodulatory effects in skin allergic responses by altering early MC activation. We will examine how ENMs alter the mechanisms of MC activation and their cross talk with other epidermal cell types using innovative live mouse intravital imaging and common techniques in novel ways. A panel of in vitro assays are proposed to further examine if ENMs exert a direct effect on MCs or act indirectly by altering paracrine signals generated by other epidermal cell types thereby suppressing or exacerbating the CHS elicitation response. This project will generate knowledge needed to assess the risk/benefit of unintended/intended ENM skin exposure and generate novel approaches for preventing allergic skin inflammation.

Public Health Relevance

Engineered nanomaterials (ENM) are increasing found in consumer products and technological applications. We discovered that ENMs topically applied to skin can modulate allergic immune responses. This finding has both increased toxicological risk concerns and therapeutic implications. In this project will investigate the cellular and molecular mechanisms of how ENMs alter skin immune responses for which little is currently understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES021492-07
Application #
9605291
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Nadadur, Srikanth
Project Start
2012-06-05
Project End
2022-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Rochester
Department
Dermatology
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Jatana, Samreen; Palmer, Brian C; Phelan, Sarah J et al. (2017) Immunomodulatory Effects of Nanoparticles on Skin Allergy. Sci Rep 7:3979
Jatana, Samreen; Palmer, Brian C; Phelan, Sarah J et al. (2017) In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation. Part Fibre Toxicol 14:12
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Mortensen, Luke J; Jatana, Samreen; Gelein, Robert et al. (2013) Quantification of quantum dot murine skin penetration with UVR barrier impairment. Nanotoxicology 7:1386-98
Zheng, Hong; Mortensen, Luke J; DeLouise, Lisa A (2013) Thiol antioxidant-functionalized CdSe/ZnS quantum dots: synthesis, characterization, cytotoxicity. J Biomed Nanotechnol 9:382-92

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