Keratinocytes (KCs) form the outer epithelial barrier of the body, protecting against
invading pathogens. Mice lacking the IL-17RA or both IL-17A and IL-17F develop spontaneous
Staphylococcus aureus skin infections. We found a marked expansion of T17 cells, comprised of RORγt-expressing γδ T cells and T helper 17 cells in the skin-draining
lymph nodes of these mice. Contradictory to previous suggestions, this expansion was
not a result of a direct negative feedback loop because we found no expansion of T17 cells in mice lacking IL-17 signaling specifically in T cells. Instead, we found
that the T17 expansion depended on the microbiota and was observed only when KCs were deficient
for IL-17RA signaling. Indeed, mice that lack IL-17RA only in KCs showed an increased
susceptibility to experimental epicutaneous infection with S. aureus together with an accumulation of IL-17A−producing γδ T cells. We conclude that deficiency
of IL-17RA on KCs leads to microbiota dysbiosis in the skin, which triggers the expansion
of IL-17A−producing T cells. Our data show that KCs are the primary target cells of
IL-17A and IL-17F, coordinating the defense against microbial invaders in the skin.
Graphical abstract
Graphical Abstract
Abbreviations:
IMQ (imiquimod), KC (keratinocyte), mLN (mesenteric lymph node), pLN (peripheral skin-draining lymph node), Th (T helper)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 01, 2023
Accepted:
January 5,
2023
Received in revised form:
December 5,
2022
Received:
April 29,
2022
accepted manuscript published online XXX; corrected proof published online XXXPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
