Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion

Nina Dickgreber, Kathryn J. Farrand, Nicholas J. Van Panhuys, Deborah A. Knight, Sara J. Mckee, Mei L. Chong, Socorro Miranda-Hernandez, Alan G. Baxter, Richard M. Locksley, Graham Le Gros, Ian F. Hermans

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substi-tuting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an "innate" phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1 cells) and Stage 2 (CD4+ CD44hi NK1.1 cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the "Th2-prone" phe-notype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.

Original languageEnglish
Pages (from-to)999-1009
Number of pages11
JournalJournal of Leukocyte Biology
Volume92
Issue number5
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Fingerprint

Natural Killer T-Cells
Interleukin-4
Thymus Gland
Cytokines
Ligands
Spleen

Keywords

  • α-galactosylceramide
  • G4 mice
  • KN2 mice
  • Thymus

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Dickgreber, N., Farrand, K. J., Van Panhuys, N. J., Knight, D. A., Mckee, S. J., Chong, M. L., ... Hermans, I. F. (2012). Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. Journal of Leukocyte Biology, 92(5), 999-1009. https://doi.org/10.1189/jlb.0512242

Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. / Dickgreber, Nina; Farrand, Kathryn J.; Van Panhuys, Nicholas J.; Knight, Deborah A.; Mckee, Sara J.; Chong, Mei L.; Miranda-Hernandez, Socorro; Baxter, Alan G.; Locksley, Richard M.; Le Gros, Graham; Hermans, Ian F.

In: Journal of Leukocyte Biology, Vol. 92, No. 5, 11.2012, p. 999-1009.

Research output: Contribution to journalArticle

Dickgreber, N, Farrand, KJ, Van Panhuys, NJ, Knight, DA, Mckee, SJ, Chong, ML, Miranda-Hernandez, S, Baxter, AG, Locksley, RM, Le Gros, G & Hermans, IF 2012, 'Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion', Journal of Leukocyte Biology, vol. 92, no. 5, pp. 999-1009. https://doi.org/10.1189/jlb.0512242
Dickgreber, Nina ; Farrand, Kathryn J. ; Van Panhuys, Nicholas J. ; Knight, Deborah A. ; Mckee, Sara J. ; Chong, Mei L. ; Miranda-Hernandez, Socorro ; Baxter, Alan G. ; Locksley, Richard M. ; Le Gros, Graham ; Hermans, Ian F. / Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. In: Journal of Leukocyte Biology. 2012 ; Vol. 92, No. 5. pp. 999-1009.
@article{63b0dd20f35a42ab9f6c7a589433cae0,
title = "Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion",
abstract = "We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substi-tuting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in na{\"i}ve animals revealed an {"}innate{"} phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1 cells) and Stage 2 (CD4+ CD44hi NK1.1 cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the {"}Th2-prone{"} phe-notype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.",
keywords = "α-galactosylceramide, G4 mice, KN2 mice, Thymus",
author = "Nina Dickgreber and Farrand, {Kathryn J.} and {Van Panhuys}, {Nicholas J.} and Knight, {Deborah A.} and Mckee, {Sara J.} and Chong, {Mei L.} and Socorro Miranda-Hernandez and Baxter, {Alan G.} and Locksley, {Richard M.} and {Le Gros}, Graham and Hermans, {Ian F.}",
year = "2012",
month = "11",
doi = "10.1189/jlb.0512242",
language = "English",
volume = "92",
pages = "999--1009",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion

AU - Dickgreber, Nina

AU - Farrand, Kathryn J.

AU - Van Panhuys, Nicholas J.

AU - Knight, Deborah A.

AU - Mckee, Sara J.

AU - Chong, Mei L.

AU - Miranda-Hernandez, Socorro

AU - Baxter, Alan G.

AU - Locksley, Richard M.

AU - Le Gros, Graham

AU - Hermans, Ian F.

PY - 2012/11

Y1 - 2012/11

N2 - We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substi-tuting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an "innate" phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1 cells) and Stage 2 (CD4+ CD44hi NK1.1 cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the "Th2-prone" phe-notype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.

AB - We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substi-tuting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an "innate" phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1 cells) and Stage 2 (CD4+ CD44hi NK1.1 cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the "Th2-prone" phe-notype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.

KW - α-galactosylceramide

KW - G4 mice

KW - KN2 mice

KW - Thymus

UR - http://www.scopus.com/inward/record.url?scp=84868333045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868333045&partnerID=8YFLogxK

U2 - 10.1189/jlb.0512242

DO - 10.1189/jlb.0512242

M3 - Article

VL - 92

SP - 999

EP - 1009

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 5

ER -