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

## TL;DR

ABCC1 protects skin dendritic cells from FITC toxicity by removing the chemical and creating a protective glutathione buffer.

## Contribution

ABCC1 protects dendritic cells from FITC toxicity through intracellular efflux and extracellular glutathione buffering.

## Key findings

- ABCC1 protects dendritic cells from FITC-induced toxicity by transporting it out of the cells.
- ABCC1 contributes to extracellular glutathione buffering, protecting surrounding cells.
- Dendritic cells rely on ABCC1 and glutathione for resistance to toxic organic molecules.

## Abstract

Adaptive immunity is critically dependent on dendritic cells (DCs) and their ability to take up foreign molecules for processing and presentation to T cells. DCs in the skin are exposed to a diversity of environmental chemicals, and whether they have mechanisms to protect themselves from chemical-induced toxicity has been unclear. In this work, we investigate the role of the multidrug resistance transporter ABCC1 in DC biology. We reveal that ABCC1 shields DCs from chemical poisoning following skin exposure to fluorescein isothiocyanate. ABCC1 is needed both cell intrinsically and cell extrinsically to achieve the full protective effect. This finding underscores a previously unrecognized reliance of DCs on ABCC1 function and opens new opportunities for therapeutic manipulation of these cells.

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 of ABCC1 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.