The skin protects the body from constant environmental threats by acting as a physical and an immunological barrier. As a consequence of this, many immune cells can be found in the skin. Antibody secreting cells are immune cells that secrete large amounts of proteins, which block the actions of toxins and invading microbes by acting as antibodies. The binding of these antibodies then leads to the activation of various immune responses. While antibody mediated immune responses are crucial for the protection against skin infections, antibodies and antibody secreting cells have also been associated with many autoimmune and inflammatory diseases. My long-range goal is to understand the role of skin ASCs in the context of host defense as well as during inflammatory skin diseases. My hypothesis is that ASC migration to skin is enhanced under inflammatory conditions, which in turn increases the local antibody concentration and that the migration of ASCs to the skin is a regulated process controlled by chemokine - chemokine receptor interactions. The objectives of this proposal are to characterize skin ASC populations and to determine the mechanism(s) responsible for ASC migration to the skin. I plan to test my hypothesis and fulfill the objectives f this application by pursuing the following specific aims;(1) Characterization of ASCs in the skin during homeostasis and inflammation (2) Profiling of skin ASC chemokine receptor expression and chemotactic responses. The rationale for the proposed research is that increasing our knowledge of ASCs found in skin and defining the mechanisms by which ASCs migrate into the skin will reveal novel targets for the treatment of various skin infections and inflammatory disorders.

Public Health Relevance

Project Antibody secreting cells are immune cells that secrete large amounts of antibodies. The purpose of this proposal is to characterize the antibody secreting cells found in the skin and to determine the mechanism(s) antibody secreting cells employ to migrate to the skin. Due to the importance of antibodies, characterizing skin antibody-secreting cells and determining how antibody secreting cells migrate to the skin could potentially establish new ideas and concepts that are of relevance for the treatment of various diseases including skin cancers, skin infections and skin autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR062451-02
Application #
8510380
Study Section
Special Emphasis Panel (ZRG1-F10B-S (20))
Program Officer
Cibotti, Ricardo
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$53,942
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Geherin, Skye A; Wilson, R Paul; Jennrich, Silke et al. (2014) CXCR4 is dispensable for T cell egress from chronically inflamed skin via the afferent lymph. PLoS One 9:e95626