Receptor-type protein tyrosine phosphatase gamma (PTPgamma), a new identifier for myeloid dendritic cells and specialized macrophages.
Protein tyrosine phosphatase (PTPgamma) is a receptor-like molecule with a known role in murine hematopoiesis. We analyzed the regulation of PTPgamma expression in the human hematopoietic system, where it was detected in human peripheral blood monocytes and dendritic cells (DCs) of myeloid and plasmacytoid phenotypes. Its expression was maintained during in vitro monocyte differentiation to dendritic cells (moDC) and was further increased after maturation with bacterial lipopolysaccharide (LPS), CD40L, and TNFalpha. But PTPgamma was absent when monocytes from the same donor were induced to differentiate in macrophages. B and T lymphocytes did not express PTPgamma. Rather, PTPgamma mRNA was expressed in primary and secondary lymphoid tissues, and the highest expression was in the spleen. PTPgamma was detected by immunohistochemistry in subsets of myeloid-derived DCs and specialized macrophages (tingible bodies, sinus and alveolar macrophages). Classic macrophages in infective or reactive granulomatous reactions did not express PTPgamma. Increased PTPgamma expression was associated with a decreased ability to induce proliferation and interferon-gamma secretion in T cells by moDCs from patients with advanced pancreatic cancer. Taken together, these results indicate that PTPgamma is a finely regulated protein in DC and macrophage subsets in vitro and in vivo.
Lissandrini
Daniele
D
Department of Pathology, University of Verona, Verona, Italy.
Vermi
William
W
Vezzalini
Marzia
M
Sozzani
Silvano
S
Facchetti
Fabio
F
Bellone
Graziella
G
Mafficini
Andrea
A
Gentili
Francesca
F
Ennas
Maria Grazia
MG
Tecchio
Cristina
C
Sorio
Claudio
C
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000201:enzymology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000943:Antigens, Differentiation; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma; C516850:PTPRG protein, human; D017027:Protein Tyrosine Phosphatases; C516851:Ptprg protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5