Innate lymphoid cells facilitate NK cell development through a lymphotoxinmediated stromal microenvironment

Tae Jin Kim, Vaibhav Upadhyay, Vinay Kumar, Kyung-Mi Lee, Yang Xin Fu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Natural killer (NK) cell development relies on signals provided from the bone marrow (BM) microenvironment. It is thought that lymphotoxin (LT) α1β2 expressed by the NK cell lineage interacts with BM stromal cells to promote NK cell development. However, we now report that a small number of RORγt+ innate lymphoid cells (ILCs), and not CD3-NK1.1+ cells, express LT to drive NK development. Similar to LT-/- or RORγt-/- mice, the mice conditionally lacking LTα1β2 on RORγt+ ILCs experience a developmental arrest at the immature NK stages, between stages of NK development to the mature NK cell stage. This developmental block results in a functional deficiency in the clearance of NK-sensitive tumor cells. Reconstitution of Thy1+ ILCs from BM or purified RORγt+ ILCs from lamina propria lymphocytes into LT-deficient RORγt+ BM cultures rescues NK cell development. These data highlight a previously undiscovered role of RORγt+ ILCs for NK cell development and define LT from ILCs as an essential molecule for the stromal microenvironment supporting NK cell development.

Original languageEnglish
Pages (from-to)1421-1431
Number of pages11
JournalJournal of Experimental Medicine
Volume211
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1

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Natural Killer Cells
Lymphotoxin-alpha
Lymphocytes
Bone Marrow
Cell Lineage
Mesenchymal Stromal Cells
Mucous Membrane
Neoplasms

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Innate lymphoid cells facilitate NK cell development through a lymphotoxinmediated stromal microenvironment. / Kim, Tae Jin; Upadhyay, Vaibhav; Kumar, Vinay; Lee, Kyung-Mi; Fu, Yang Xin.

In: Journal of Experimental Medicine, Vol. 211, No. 7, 01.01.2014, p. 1421-1431.

Research output: Contribution to journalArticle

Kim, Tae Jin ; Upadhyay, Vaibhav ; Kumar, Vinay ; Lee, Kyung-Mi ; Fu, Yang Xin. / Innate lymphoid cells facilitate NK cell development through a lymphotoxinmediated stromal microenvironment. In: Journal of Experimental Medicine. 2014 ; Vol. 211, No. 7. pp. 1421-1431.
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