{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:32:10Z","timestamp":1787869930920,"version":"build-2784847793"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Lactic acid bacteria (LAB) are well known for their beneficial effects on the regulation of immune responses and host protection against microbial infections. We previously reported that heat-killed\n                      <jats:italic>Enterococcus faecalis<\/jats:italic>\n                      strain KH2 (heat-killed KH2), a species of LAB, enhances inflammatory responses at wound sites and accelerates the skin wound healing process. In this study, we aimed to clarify the pathway underlying the wound-healing effects of heat-killed KH2. We focused on CARD9, a common adaptor molecule for C-type lectin receptors and Dectin-2, the upstream receptor for this adaptor molecule.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Four full-thickness dermal wounds were created on the backs of wild-type (WT) mice, CARD9 KO mice, and Dectin-2 KO mice, and the effects of heat-killed KH2 administration were examined. We analyzed the percent wound closure, re-epithelialization, granulation tissue formation, and the production of inflammatory cytokines and chemokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Heat-killed KH2 administration enhanced wound closure, granulation tissue formation, and re-epithelialization in WT mice. However, these effects were absent in heat-killed KH2-treated CARD9 KO mice. Similar results were observed in the migration of neutrophils and the production of TNF-\u03b1, IL-6, KC, and MIP-2 in heat-killed KH2-treated CARD9 KO mice. Furthermore, heat-killed KH-2 induced activation of reporter cells expressing Dectin-2. Finally, heat-killed KH-2 treatment in Dectin-2 KO mice did not promote skin wound healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results suggest that recognition of heat-killed KH2 by Dectin-2 may activate CARD9-mediated signaling, which may contribute to the promotion of skin wound healing through KH2 treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1550934","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T01:20:30Z","timestamp":1749691230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2"],"prefix":"10.3389","volume":"16","author":[{"given":"Shiho","family":"Kurosaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Tanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena","family":"Takayashiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikue","family":"Sone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinyo","family":"Ishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimichi","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1152\/physrev.00067.2017","article-title":"Wound 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