FcepsilonRI-dependent gene expression in human mast cells is differentially controlled by T helper type 2 cytokines.
BACKGROUND
Mast cells (MCs) proliferate in response to T(H)2 cytokines and express genes de novo after activation. Limited information is available concerning the interplay between these events.


OBJECTIVE
We explored the potential for T(H)2 cytokines to alter activation-dependent gene expression by MCs.


METHODS
Cord blood-derived human (h)MCs maintained in stem cell factor (SCF) alone were compared with replicates treated with IL-4, IL-5, or IL-9, respectively, for their patterns of FcepsilonRI-dependent gene induction using microarray technology.


RESULTS
Activation of SCF-treated hMCs upregulated their expression of roughly 140 transcripts at 2 hours, including genes involved in cell cycle progression and arrest. Each cytokine substantially modified this profile; approximately 800 inducible genes apiece were controlled by IL-5 or IL-9, whereas 169 inducible genes were controlled by IL-4. IL-4 favored the induction of cytokines and of genes associated with cell growth arrest (GADD34, GAS-1, CIDE-A, INK4D, and BAX) and completely abolished the enhanced proliferation observed in the other 3 groups after activation. Conversely, IL-5 priming induced preferential upregulation of genes involved in cell proliferation and did not abolish thymidine incorporation.


CONCLUSIONS
T(H)2 cytokines differentially modulate gene induction in hMCs after FcepsilonRI cross-linkage. IL-4 uniquely controls cytokine gene expression by hMCs and might also limit their activation-driven proliferation.
Lora
José M
JM
Department of Immunobiology and Inflammation, Cambridge, MA, USA.
Al-Garawi
Amal
A
Pickard
Michael D
MD
Price
Kursteen S
KS
Bagga
Savita
S
Sicoli
Jaclyn
J
Hodge
Martin R
MR
Gutiérrez-Ramos
José-Carlos
JC
Briskin
Michael J
MJ
Boyce
Joshua A
JA
D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D005312:Fetal Blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019089:Stem Cell Factor / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation
D016207:Cytokines; D011961:Receptors, Fc; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D007073:Immunoglobulin E