The expression pattern of the ITIM-bearing lectin CLECSF6 in neutrophils suggests a key role in the control of inflammation.
In our study of the modulation of the expression of inflammation-related genes in neutrophils, we have found a gene called CLECSF6 (C-type lectin superfamily 6). CLECSF6 expresses two mRNA species at low levels in resting neutrophils. Here, we describe for the first time the sequence of the short mRNA version. It lacks amino acids that are likely to affect the functionality of its protein product. GM-CSF, IL-3, IL-4, and IL-13 caused an accumulation of the short CLECSF6 mRNA in neutrophils. The surface expression of the CLECSF6 protein was reduced by TNF-alpha, IL-1alpha, LPS, and Matrigel. CLECSF6 bears the immunoreceptor tyrosine-based inhibition motif (ITIM) involved in signal transduction resulting in the inhibition of leukocyte activation. We propose that some neutrophil activators modulate the expression of CLECSF6 at the mRNA (GM-CSF, IL-3, IL-4, and IL-13) or protein (TNF-alpha, IL-1alpha, LPS, and Matrigel) levels in ways that block ITIM-based transduction of anti-inflammatory signals and therefore promote inflammation.
Richard
Manon
M
Laboratoire de Recherche sur l'Arthrite et l'Inflammation, Department of Medicine, Centre Hospitalier de l'Université Laval, 2705 Boulevard Laurier, Sainte-Foy, Québec, Canada G1V 4G2.
Veilleux
Patricia
P
Rouleau
Michèle
M
Paquin
Robert
R
Beaulieu
André D
AD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002454:Cell Differentiation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology; D037102:Lectins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic; D014158:Transcription, Genetic / Q000187:drug effects
C423004:CLEC4A protein, human; D007378:Interleukins; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor