Selective estrogen receptor modulators in T cell development and T cell dependent inflammation

Area of Science:

• Immunology
• Endocrinology
• Pharmacology

Background:

• Selective estrogen receptor modulators (SERMs) are used for postmenopausal osteoporosis.
• Estrogen (17β-estradiol, E2) influences T cell development and inflammation.
• Third-generation SERMs, lasofoxifene (las) and bazedoxifene (bza), have minimal estrogenic side effects.

Purpose of the Study:

• To investigate the effects of lasofoxifene and bazedoxifene on T lymphopoiesis and T cell-dependent inflammation.
• To compare the effects of third-generation SERMs with estrogen and a second-generation SERM (raloxifene).

Main Methods:

• Ovariectomized mice (ovx) were treated with vehicle, E2, raloxifene (ral), lasofoxifene (las), or bazedoxifene (bza).
• Effects on thymus weight, thymic T cell populations, and delayed-type hypersensitivity (DTH) response were assessed.

Main Results:

• E2 reduced thymus weight, altered T cell populations, and suppressed DTH response.
• Raloxifene and lasofoxifene, but not bazedoxifene, decreased thymus weight.
• None of the tested SERMs affected thymic T cell populations or DTH inflammation.

Conclusions:

• Lasofoxifene and bazedoxifene do not significantly affect T lymphopoiesis.
• These SERMs do not alter T cell-dependent inflammation.
• Findings suggest lasofoxifene and bazedoxifene have a distinct immunomodulatory profile compared to estrogen.