%0 Journal Article
%T TGF¦Â signaling plays a critical role in promoting alternative macrophage activation
%A Dapeng Gong
%A Wei Shi
%A Sun-ju Yi
%A Hui Chen
%A John Groffen
%A Nora Heisterkamp
%J BMC Immunology
%D 2012
%I BioMed Central
%R 10.1186/1471-2172-13-31
%X Vav1-Cre x T¦ÂRIIfx/fx mice, lacking T¦ÂRII function in hematopoietic cells, exhibited uncontrolled pulmonary inflammation and developed a lethal autoimmune syndrome at young age. This was accompanied by significantly increased numbers of splenic neutrophils and T cells as well as elevated hepatic macrophage infiltration and bone marrow monocyte counts. T¦ÂRII-/- CD4+ and CD8+ T-cells in the lymph nodes and spleen expressed increased cell surface CD44, and CD69 was also higher on CD4+ lymph node T-cells. Loss of T¦ÂRII in bone marrow-derived macrophages (BMDMs) did not affect the ability of these cells to perform efferocytosis. However, these cells were defective in basal and IL-4-induced arg1 mRNA and Arginase-1 protein production. Moreover, the transcription of genes that are typically upregulated in M2-polarized macrophages, such as ym1, mcr2 and mgl2, was also decreased in peritoneal macrophages and IL-4-stimulated T¦ÂRII-/- BMDMs. We found that cell surface and mRNA expression of Galectin-3, which also regulates M2 macrophage polarization, was lower in T¦ÂRII-/- BMDMs. Very interestingly, the impaired ability of these null mutant BMDMs to differentiate into IL-4 polarized macrophages was Stat6- and Smad3-independent, but correlated with reduced levels of phospho-Akt and ¦Â-catenin.Our results establish a novel biological role for TGF¦Â signaling in controlling expression of genes characteristic for alternatively activated macrophages. We speculate that lack of T¦ÂRII signaling reduces the anti-inflammatory M2 phenotype of macrophages because of reduced expression of these products. This would cause defects in the ability of the M2 macrophages to negatively regulate other immune cells such as T-cells in the lung, possibly explaining the systemic inflammation observed in Vav1-Cre x T¦ÂRIIfx/fx mice.
%K TGF¦Â
%K Macrophage polarization
%K Lung
%K Alveolar macrophage
%K M1
%K M2
%K Hematopoietic
%K Inflammation
%K TGFBR2
%K LGALS3
%U http://www.biomedcentral.com/1471-2172/13/31/abstract