IL-4-independent regulation of in vivo IL-9 expression.
We focused on the role of IL-4 in the regulation of the Th2 cytokine IL-9. In vivo, IL-9 mRNA was detected in lymph nodes after immunization with soluble Ags. IL-9 expression preceded that of IL-4, and was not affected in IL-4 knockout mice. In contrast, a significant decrease of IL-9 message was observed in IL-10-deficient mice, indicating a role for this cytokine in the induction of IL-9 production. Treatment with anti-CD4 Ab and analysis of purified CD4 cells confirmed that IL-9 was produced by CD4+ cells. Moreover, similarly to what has been reported for IL-4, IL-9 message induction was strongly decreased by infection with lactate dehydrogenase-elevating virus. IL-9 mRNA was also detected after in vivo stimulation with anti-CD3 Ab. In this model, IL-9 expression followed that of IL-4, but was not reduced in IL-4-deficient mice. This contrasts with in vitro stimulation in which, as reported in humans, IL-9 expression in lymphocytes incubated with anti-CD3 Ab and costimulatory molecules appeared as a late event, and was partly dependent on IL-4. In vitro IL-9 secretion was reduced significantly by addition of anti-IL-4 Ab, as well as in lymphocytes from IL-4 gene-deficient mice. Taken together, our results indicate that the Th2 cytokine IL-9 can be expressed by both IL-4-dependent and -independent pathways.
Monteyne
P
P
Unit of Experimental Medicine, Catholic University of Louvain and International Institute for Cellular and Molecular Pathology, Brussels, Belgium.
Renauld
J C
JC
Van Broeck
J
J
Dunne
D W
DW
Brombacher
F
F
Coutelier
J P
JP
D000818:Animals; D005786:Gene Expression Regulation; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016906:Interleukin-9 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D016906:Interleukin-9; D015847:Interleukin-4