Adverse Outcome Pathway on inhibition of calcineurin activity leading to impaired T-cell dependent antibody response

[摘要] The present AOP describes the inhibition of calcineurin activity resulting in impaired T-Cell Dependent Antibody Response (TDAR). Calcineurin (CN), a protein phosphatase, is known to impair immune function when its phosphatase activation is inhibited. CN inhibitors (CNIs) inhibit CN phosphatase activity to suppress many kinds of immune functions and have been used in the medical domain to prevent hyper immune reactions. However, CNIs are reported to also induce immunosuppression-derived adverse effects such as increased frequency and/or severity of infections and increased tumor incidences. CNIs might affect several T-cell derived immune functions to induce compromised host. Among the affected immune functions, T-cell dependent antibody response (TDAR) is an important factor to resist infections and thought to be the useful endpoint on evaluating immunotoxicity of chemicals; therefore, this AOP describes the linkage between the inhibition of CN activity and impairment of TDAR.

[发布日期] 2021-10-15 [发布机构] Organisation for Economic Co-operation and Development

[学科分类] 社会科学、人文和艺术（综合）