CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans
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CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans. / Martrus, Glòria; Goebels, Hanna; Langeneckert, Annika E; Kah, Janine; Flomm, Felix; Ziegler, Annerose E; Niehrs, Annika; Löbl, Sebastian M; Russu, Kristina; Hess, Leonard U; Salzberger, Wilhelm; Poch, Tobias; Nashan, Björn; Schramm, Christoph; Oldhafer, Karl J; Dandri, Maura; Koch, Martina; Lunemann, Sebastian; Altfeld, Marcus.
in: FRONT IMMUNOL, Jahrgang 10, 2019, S. 1247.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans
AU - Martrus, Glòria
AU - Goebels, Hanna
AU - Langeneckert, Annika E
AU - Kah, Janine
AU - Flomm, Felix
AU - Ziegler, Annerose E
AU - Niehrs, Annika
AU - Löbl, Sebastian M
AU - Russu, Kristina
AU - Hess, Leonard U
AU - Salzberger, Wilhelm
AU - Poch, Tobias
AU - Nashan, Björn
AU - Schramm, Christoph
AU - Oldhafer, Karl J
AU - Dandri, Maura
AU - Koch, Martina
AU - Lunemann, Sebastian
AU - Altfeld, Marcus
PY - 2019
Y1 - 2019
N2 - Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as liver-resident macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well-characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14hiCD16lo and higher frequencies of CD14int-hiCD16int Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a+ Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12, and IL-10 production, but responded less to additional in vitro TLR stimulation. In contrast, intrahepatic CD49a- Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a- monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a+, VSIG4+, and/or MARCO+ Mφ in human livers, and demonstrated that intrahepatic CD49a+ Mφ differed in phenotype and function from intrahepatic CD49a- Mφ as well as from peripheral blood-derived monocytes.
AB - Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as liver-resident macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well-characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14hiCD16lo and higher frequencies of CD14int-hiCD16int Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a+ Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12, and IL-10 production, but responded less to additional in vitro TLR stimulation. In contrast, intrahepatic CD49a- Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a- monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a+, VSIG4+, and/or MARCO+ Mφ in human livers, and demonstrated that intrahepatic CD49a+ Mφ differed in phenotype and function from intrahepatic CD49a- Mφ as well as from peripheral blood-derived monocytes.
U2 - 10.3389/fimmu.2019.01247
DO - 10.3389/fimmu.2019.01247
M3 - SCORING: Journal article
C2 - 31231382
VL - 10
SP - 1247
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -