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Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Generation and Culturing of Primary Human Keratinocytes from Adult Skin

Published on: December 22, 2017

When SLC46A2 delivers cargo into keratinocytes.

Xinxin Wang¹, Yuping Lai²

¹Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, P.R. China.

|May 10, 2023

Summary

Skin cells use SLC46A2 to sense bacterial fragments, activating NOD1 to cause inflammation in conditions like psoriasis. This finding clarifies how extracellular bacteria trigger keratinocyte responses.

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Area of Science:

Immunology
Dermatology
Microbiology

Background:

Pattern recognition receptors NOD1 and NOD2 are crucial for sensing bacterial components.
The precise mechanism by which extracellular bacteria trigger keratinocyte inflammation via these receptors is not fully understood.
Psoriasis involves skin inflammation potentially linked to microbial sensing pathways.

Purpose of the Study:

To elucidate the mechanism of bacterial muropeptide sensing by keratinocytes.
To identify the cellular components involved in NOD1 activation by extracellular bacteria.
To understand the role of this pathway in keratinocyte-driven skin inflammation.

Main Methods:

Investigated the uptake of diaminopimelic acid (DAP)-muropeptides in keratinocytes.
Utilized genetic and biochemical approaches to identify the transporter involved.
Assessed the activation of NOD1 signaling and downstream inflammatory responses.

Main Results:

Identified solute carrier 46A2 (SLC46A2) as the transporter responsible for delivering DAP-muropeptides into keratinocyte cytosol.
Demonstrated that SLC46A2-mediated delivery is essential for NOD1 activation.
Showed that this pathway drives keratinocyte inflammation, relevant to psoriasis pathogenesis.

Conclusions:

SLC46A2 facilitates the cytosolic delivery of bacterial DAP-muropeptides, crucial for NOD1 activation in keratinocytes.
This mechanism explains how extracellular bacteria can induce skin inflammation.
Targeting the SLC46A2-NOD1 axis may offer new therapeutic strategies for inflammatory skin diseases like psoriasis.