Transnuclear mice reveal Peyer's patch iNKT cells that regulate B‐cell class switching to IgG1

• Eleanor Clancy‐Thompson ^[2] ; Gui Zhen Chen ^[2] ; Nelson M LaMarche ^[3] ; Lestat R Ali ^[2] ; Hee‐Jin Jeong ^[1] ; Stephanie J Crowley ^[2] ; Kelly Boelaars ^[4] ; Michael B Brenner ^[3] ; Lydia Lynch ^[3] ; Stephanie K Dougan ^[5]
  1. [1] Hongik University

     Hongik University

     Corea del Sur

     
  2. [2] 1 Department of Cancer Immunology and Virology Dana‐Farber Cancer Institute Boston MA USA
  3. [3] 2 Department of Rheumatology Brigham and Women's Hospital Boston MA USA; 3 Program in Immunology Harvard Medical School Boston MA USA
  4. [4] 1 Department of Cancer Immunology and Virology Dana‐Farber Cancer Institute Boston MA USA; 4 VU University Amsterdam Amsterdam The Netherlands
  5. [5] 1 Department of Cancer Immunology and Virology Dana‐Farber Cancer Institute Boston MA USA; 3 Program in Immunology Harvard Medical School Boston MA USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 14, 2019
• Idioma: inglés
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  • Tissue‐resident iNKT cells maintain tissue homeostasis and peripheral surveillance against pathogens; however, studying these cells is challenging due to their low abundance and poor recovery from tissues. We here show that iNKT transnuclear mice, generated by somatic cell nuclear transfer, have increased tissue resident iNKT cells. We examined expression of PLZF, T‐bet, and RORγt, as well as cytokine/chemokine profiles, and found that both monoclonal and polyclonal iNKT cells differentiated into functional subsets that faithfully replicated those seen in wild‐type mice. We detected iNKT cells from tissues in which they are rare, including adipose, lung, skin‐draining lymph nodes, and a previously undescribed population in Peyer's patches (PP). PP‐NKT cells produce the majority of the IL‐4 in Peyer's patches and provide indirect help for B‐cell class switching to IgG1 in both transnuclear and wild‐type mice. Oral vaccination with α‐galactosylceramide shows enhanced fecal IgG1 titers in iNKT cell‐sufficient mice. Transcriptional profiling reveals a unique signature of PP‐NKT cells, characterized by tissue residency. We thus define PP‐NKT as potentially important for surveillance for mucosal pathogens.