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

Dickgreber, Nina, Farrand, Kathryn J., van Panhuys, Nicholas, Knight, Deborah A., McKee, Sara J., Chong, Mei L., Miranda-Hernandez, Socorro, Baxter, Alan G., Locksley, Richard M., Le Gros, Graham, and Hermans, Ian F. (2012) Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion. Journal of Leukocyte Biology, 92 (5). pp. 999-1009.

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Abstract

We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting 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" phenotype 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.

Item ID: 25580
Item Type: Article (Refereed Research - C1)
ISSN: 1938-3673
Funders: New Zealand Health Research Council, Marjorie Barclay Trust
Date Deposited: 18 Mar 2013 01:36
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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