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Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis

Journal of Allergy and Clinical Immunology, ISSN: 0091-6749, Vol: 147, Issue: 5, Page: 1764-1777
2021
  • 28
    Citations
  • 0
    Usage
  • 36
    Captures
  • 0
    Mentions
  • 23
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    28
  • Captures
    36
  • Social Media
    23
    • Shares, Likes & Comments
      23
      • Facebook
        23

Article Description

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). We aimed to investigate the role of NKT cells in AD development, especially in skin. 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. 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. CXCR4 + tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.

Bibliographic Details

Sun, ZhengWang; Kim, Ji Hye; Kim, Seo Hyeong; Kim, Hye Ran; Zhang, KeLun; Pan, Youdong; Ko, Min Kyung; Kim, Bo Mi; Chu, Howard; Lee, Hee Ra; Kim, Hye Li; Kim, Ji Hyung; Fu, Xiujun; Hyun, Young-Min; Yun, Ki Na; Kim, Jin Young; Lee, Dong Won; Song, Seung Yong; Lin, Charles P; Clark, Rachael A; Lee, Kwang Hoon; Kupper, Thomas S; Park, Chang Ook

Elsevier BV

Medicine; Immunology and Microbiology

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