IL-4 selectively enhances FcgammaRIII expression and signaling on mouse mast cells.
Fc receptors for IgG (FcgammaR) are widely expressed in the hematopoietic system and mediate a variety of inflammatory responses. There are two functional classes of FcgammaR, activation and inhibitory receptors. Since IgG immune complexes (IgG IC) bind each class with similar affinity, co-expression of these receptors leads to their co-ligation. Thus, expression levels of this antagonistic pair play a critical role in determining the cellular response. Murine mast cells co-express the activation receptor FcgammaRIII and the inhibitory receptor FcgammaRIIb and can be activated by IgG IC. Mast cell activation contributes to allergic and other inflammatory diseases-particularly those in which IgG IC may play important roles. Using mouse bone marrow-derived mast cells, we report that IL-4 selectively increases FcgammaRIII expression without altering FcgammaRIIb. This enhanced expression could be induced by Stat6 activation alone, and appeared to be mediated in part by increased FcgammaRIIIalpha protein synthesis without significant changes in transcription. The increase in FcgammaRIII expression was functionally significant, as it was matched by enhanced FcgammaR-mediated degranulation and cytokine production. Selective regulation of mast cell FcgammaR by interleukin-4 could alter inflammatory IgG responses and subsequently disease severity and progression.
Chong
Hey Jin
HJ
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA.
Andrew Bouton
L
L
Bailey
Daniel P
DP
Wright
Harry
H
Ramirez
Carlos
C
Gharse
Anita
A
Oskeritzian
Carole
C
Xia
Han Zhang
HZ
Zhu
Jinfang
J
Paul
William E
WE
Kepley
Chris
C
Schwartz
Lawrence B
LB
Ryan
John J
JJ
D000818:Animals; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000502:physiology
D012333:RNA, Messenger; D017452:Receptors, IgG; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4