G6b-B cell surface inhibitory receptor expression is highly restricted to CD4+ T-cells and induced by interleukin-4-activated STAT6 pathway.
The G6b-B gene encodes a novel cell surface receptor of the immunoglobulin superfamily that activates inhibitory signaling pathways by triggering SHP-1/SHP-2 via immunoreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic domain. We previously identified decreased G6b-B expression in peripheral blood mononuclear cells (PBMC) during acute cellular cardiac allograft rejection. We studied the expression of G6b-B in different human mononuclear cell populations and its regulation. Real-time polymerase chain reaction (PCR) revealed that G6b-B mRNA is higher in CD4+ T cells or monocytes, but is not different between CD25+ CD4+ T cells and CD25- CD4+ T cells. G6b-B mRNA was increased in CD4+ T cells in presence of interleukin-4 in dose- and time-dependent manners. To understand the regulatory mechanism, we analyzed a 1.9-kb 5'-flanking region of the G6b-B translation start site and found a putative cis-acting element for Signal Transducer and Activator of Transcription (STAT)-6. Luciferase-reporter-gene-assay and electrophoretic mobility shift assays identified the STAT6 site as necessary for the induction of G6b-B by IL-4. Our study demonstrates that G6b-B expression is highly restricted to peripheral CD4+ T cells and up-regulated by the IL-4-induced STAT6 pathway, strongly suggesting that G6b-B is involved in regulation of the immune response by CD4+ T cell-mediated and IL-4 induced regulatory mechanisms.
Department of Medicine, Division of Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Jianfeng
J
Li
Martin
M
Cadeiras
Manuel
M
Prinz von Bayern
Lining
L
Zhang
Adriana I
AI
Colovai
Russell
R
Dedrick
Eric A
EA
Jaffe
Nicole
N
Suciu-Foca
Mario C
MC
Deng
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism*
C119883:MPIG6B protein, human; D011971:Receptors, Immunologic; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4