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

Hiroyuki Komatsu, Junichiro Sugimoto, Ken Goto, Kiyoshi Kushima, Naohisa Tsutsui, Shigeru Hisada, Shiho Ito, Tadashi Kosaka, Takumi Ohishi, Yasuharu Otsubo and Yoshihiro Takahashi
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Hiroyuki Komatsu: The Japanese Society of Immunotoxicology
Junichiro Sugimoto: The Japanese Society of Immunotoxicology
Ken Goto: The Japanese Society of Immunotoxicology
Kiyoshi Kushima: The Japanese Society of Immunotoxicology
Naohisa Tsutsui: The Japanese Society of Immunotoxicology
Shigeru Hisada: The Japanese Society of Immunotoxicology
Shiho Ito: The Japanese Society of Immunotoxicology
Tadashi Kosaka: The Japanese Society of Immunotoxicology
Takumi Ohishi: The Japanese Society of Immunotoxicology
Yasuharu Otsubo: The Japanese Society of Immunotoxicology
Yoshihiro Takahashi: The Japanese Society of Immunotoxicology

No 18, OECD Series on Adverse Outcome Pathways from OECD Publishing

Abstract: 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.

Date: 2021-10-15
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