title: Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).
abstract: Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Siebenhaar
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Sharov
authors.forename: Eva M J
authors.initials: EM
authors.lastname: Peters
authors.forename: Tatyana Y
authors.initials: TY
authors.lastname: Sharova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Syska
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Mardaryev
authors.forename: Pia
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Botchkarev
mesh_terms: D000506:Alopecia Areata / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D018859:Hair Follicle / Q000276:immunology* / Q000294:innervation / Q000473:pathology; D007155:Immunologic Factors / Q000276:immunology* / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D015260:Neprilysin / Q000235:genetics; D009412:Nerve Fibers / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013373:Substance P / Q000276:immunology* / Q000494:pharmacology
chemical_list: D007155:Immunologic Factors; D018040:Receptors, Neurokinin-1; D013373:Substance P; D053804:Granzymes; C509214:Gzmb protein, mouse; D015260:Neprilysin