Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).

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Animals, Autoimmune-Diseases, CD8-Positive-T-Lymphocytes, Cell-Degranulation, Disease-Models-Animal, Gene-Expression, Granzymes, Hair-Follicle, Immunologic-Factors, Mast-Cells, Mice-Inbred-C3H, Neprilysin, Nerve-Fibers, Receptors-Neurokinin-1, Signal-Transduction, Substance-P

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J Invest Dermatol 2007 Jun; 127(6):1489-97.


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.