title: Selective estrogen receptor modulators in T cell development and T cell dependent inflammation.
abstract: Lasofoxifene (las) and bazedoxifene (bza) are third generation selective estrogen receptor modulators (SERMs) with minimal estrogenic side effects, approved for treatment of postmenopausal osteoporosis. T cells are involved in the pathology of postmenopausal osteoporosis and previous studies have established an important role for 17β-estradiol (E2) in T cell development and function. E2 causes a drastic thymic atrophy, alters the composition of thymic T cell populations, and inhibits T cell dependent inflammation. In contrast, the second generation SERM raloxifene (ral) lacks these properties. Although las and bza are drugs approved for treatment of postmenopausal bone loss, it is of importance to study their effects on other biological aspects in order to extend the potential use of these compounds. Therefore, the aim of this study was to investigate if treatment with las and bza affects T lymphopoiesis and T cell dependent inflammation. C57Bl6 mice were ovariectomized (ovx) and treated with vehicle, E2, ral, las or bza. As expected, E2 reduced both thymus weight and decreased the proportion of early T cell progenitors while increasing more mature T cell populations in the thymus. E2 also suppressed the T cell dependent delayed-type hypersensitivity (DTH) reaction to oxazolone (OXA). Ral and las, but not bza, decreased thymus weight, while none of the SERMs had any effects on T cell populations in the thymus or on inflammation in DTH. In conclusion, this study shows that treatment with las or bza does not affect T lymphopoiesis or T cell dependent inflammation.
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: angelina.bernardi@rheuma.gu.se.
authors.forename: Angelina I
authors.initials: AI
authors.lastname: Bernardi
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: annica.andersson@rheuma.gu.se.
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: alexandra.stubelius@rheuma.gu.se.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stubelius
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: louise.grahnemo@gu.se.
authors.forename: Louise
authors.initials: L
authors.lastname: Grahnemo
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: hans.carlsten@rheuma.gu.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: ulrika.islander@gu.se.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D038041:Lymphopoiesis / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D011960:Receptors, Estrogen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen
keywords: Delayed-type hypersensitivity; Estrogen; Selective estrogen receptor modulators; T cell development