REVIEW article
Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1646719
Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ
Provisionally accepted
- 1The Ohio State University, Columbus, United States
- 2nationwide children's hospital, Columbus, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Natural killer (NK) cells are lymphoid-derived cells that play a critical role in bridging innate and adaptive immunity. Given their ability to recognize and directly kill targets possessing missing or altered self-proteins and to induce indirect killing via recruitment of adaptive immunity, they are in a unique position to modulate host immunologic responses. These complex immune sentinels typically circulate in the peripheral blood and/or reside in lymphoid tissues. As the largest organ, human skin functions in front line immunological defense, though it has not historically been categorized as lymphoid tissue. Whether tissue-resident ILC populations originally derive from conventional circulating NK cells, or whether they interface as developmentally distinct entities with phenotypic overlap within particular inflammatory contexts remains a subject of ongoing investigation. This review seeks to consolidate the currently available literature regarding NK cell and ILC skin homing and innate immune function in healthy vs. lesional human skin (including infection, inflammatory/autoimmune conditions, and cutaneous malignancy). Importantly, we elucidate significant gaps in the understanding of the complex role for NK cells in skin homeostasis and pathology, and posit unique opportunities the accessibility of this secondary lymphoid organ provides for translational studies to improve our understanding of cutaneous immunity.
Keywords: Natural Killer cells, innate lymphoid cells, Cutaneous disease, skin Transcription factors Eomes [6-7] T-bet [8-9] Hobit [22] T-bet [9, 23] GATA3 [9, 31] RORγT [9] +/-Eomes & Tbet [42], Tcf1 [43] Chemotactic and homing molecules CCL3, CCl4
Received: 13 Jun 2025; Accepted: 15 Jul 2025.
Copyright: © 2025 Johnson and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kirsten M Johnson, The Ohio State University, Columbus, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.