title: Amyloid precursor family proteins are expressed by thymic and lymph node stromal cells but are not required for lymphocyte development.
abstract: Pharmacological inhibitors that block amyloid precursor protein (APP) cleavage and the formation of senile plaques are under development for the treatment of familial Alzheimer's disease. Unfortunately, many inhibitors that block gamma-secretase-mediated cleavage of APP also have immunosuppressive side effects. In addition to APP, numerous other proteins undergo gamma-secretase-mediated cleavage. In order to develop safer inhibitors, it is necessary to determine which of the gamma-secretase substrates contribute to the immunosuppressive effects. Because APP family members are widely expressed and are reported to influence calcium flux, transcription and apoptosis, they could be important for normal lymphocyte maturation. We find that APP and amyloid precursor-like protein 2 are expressed by stromal cells of thymus and lymph nodes, but not by lymphocytes. Although signals provided by thymic stromal cells are critical for normal T cell differentiation, lymphocyte development proceeds unperturbed in mice deficient for these APP family members.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892-0420, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Laky
authors.forename: Willem
authors.initials: W
authors.lastname: Annaert
authors.forename: B J
authors.initials: BJ
authors.lastname: Fowlkes
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000276:immunology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D053829:Amyloid Precursor Protein Secretases