ABCC1 protects skin dendritic cells from FITC-induced toxicity by efflux and extracellular glutathione buffering

• 成果类型: Article
• 署名作者: Knopper, Konrad; Rao, Anshul; An, Jinping; Cyster, Jason G.
• 署名单位: Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2538155123
• 发表日期: 2026-03-10
• 页码: e2538155123
• 关键词: dendritic cells; apoptosis; cell trafficking; skin; transporter; FLUORESCEIN ISOTHIOCYANATE; macropinocytosis; mechanisms; migration; mrp1

摘要

Dendritic cell (DC) migration is critical for initiating adaptive immune responses. Previous work suggested a role for ATP-binding cassette transporter C1 (ABCC1) in skin DC migration following cutaneous fluorescein isothiocyanate (FITC) exposure, but the precise mechanism involved was unclear. Here, we establish that the primary contribution ofABCC1 to skin DC function following FITC exposure is not modulation of migration, but enhancement of survival. Our findings demonstrate that ABCC1 operates on a dual level: Intracellularly, by transporting toxic FITC and fluorescein out of DCs, and extracellularly, by contributing to a glutathione (GSH) buffer zone that protects surrounding cells. DCs are particularly susceptible to FITC-mediated toxicity, possibly due to their high endocytic activity. This study elucidates the critical dependence of DCs on ABCC1 and extracellular GSH for resistance to toxic organic molecules and thereby identifies potential therapeutic avenues targeting ABCC1 to modulate immune responses.