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

Eleanor Clancy-Thompson, Gui Zhen Chen, Nelson M. LaMarche, Lestat R. Ali, Hee Jin Jeong, Stephanie J. Crowley, Kelly Boelaars, Michael B. Brenner, Lydia Lynch, Stephanie K. Dougan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere101260
JournalEMBO Journal
Volume38
Issue number14
DOIs
StatePublished - Jul 15 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

Keywords

  • IL-4, tissue-resident iNKT cells
  • Peyer's patches
  • oral vaccines
  • transnuclear mice

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