ZhengWang Sun1, Ji Hye Kim2, Seo Hyeong Kim2, Hye Ran Kim1, KeLun Zhang2, Youdong Pan3, Min Kyung Ko1, Bo Mi Kim1, Howard Chu1, Hee Ra Lee1, Hye Li Kim2, Ji Hyung Kim4, Xiujun Fu5, Young-Min Hyun6, Ki Na Yun7, Jin Young Kim7, Dong Won Lee8, Seung Yong Song8, Charles P Lin5, Rachael A Clark3, Kwang Hoon Lee9, Thomas S Kupper10, Chang Ook Park11. 1. Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. 2. Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Project, Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 4. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea. 5. Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 6. Brain Korea 21 Project, Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, Korea; Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. 7. Biomedical Omics Group, Korea Basic Science Institute, Ochang, Korea. 8. Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University College of Medicine, Seoul, Korea. 9. Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Project, Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: kwanglee@yuhs.ac. 10. Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: tkupper@bwh.harvard.edu. 11. Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 Project, Graduate School of Medical Science, Yonsei University College of Medicine, Seoul, Korea; Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: copark@yuhs.ac.
Abstract
BACKGROUND: Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD). OBJECTIVE: We aimed to investigate the role of NKT cells in AD development, especially in skin. METHODS: Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy-controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4-conditionally deficient or CXCL12 transgenic mice. RESULTS: CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD. CONCLUSIONS: CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
BACKGROUND: Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD). OBJECTIVE: We aimed to investigate the role of NKT cells in AD development, especially in skin. METHODS: Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy-controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4-conditionally deficient or CXCL12 transgenic mice. RESULTS: CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD. CONCLUSIONS: CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
Authors: J J Campbell; G Haraldsen; J Pan; J Rottman; S Qin; P Ponath; D P Andrew; R Warnke; N Ruffing; N Kassam; L Wu; E C Butcher Journal: Nature Date: 1999-08-19 Impact factor: 49.962
Authors: Mayte Suárez-Fariñas; Benjamin Ungar; Joel Correa da Rosa; David A Ewald; Mariya Rozenblit; Juana Gonzalez; Hui Xu; Xiuzhong Zheng; Xiangyu Peng; Yeriel D Estrada; Stacey R Dillon; James G Krueger; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Date: 2015-03-31 Impact factor: 10.793
Authors: Lee A Albacker; Vinod Chaudhary; Ya-Jen Chang; Hye Young Kim; Ya-Ting Chuang; Muriel Pichavant; Rosemarie H DeKruyff; Paul B Savage; Dale T Umetsu Journal: Nat Med Date: 2013-09-01 Impact factor: 53.440