Solute carrier 11A1 is expressed by innate lymphocytes and augments their activation

Solute carrier 11A1 (SLC11A1) is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1) and the Bcg/Lsh/Ity locus. SLC11A1 was thought to be exclusively expressed in monocyte/macrophages and to have roles in phagosome maturation and cell activation...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2013-04, Vol.190 (8), p.4263-4273
Main Authors: Hedges, Jodi F, Kimmel, Emily, Snyder, Deann T, Jerome, Maria, Jutila, Mark A
Format: Article
Language:English
Subjects:
Animals
Cation Transport Proteins - biosynthesis
Cation Transport Proteins - genetics
Cation Transport Proteins - physiology
Cattle
Humans
Immunity, Innate - genetics
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Mice
Mice, 129 Strain
Mice, Knockout
Phosphorylation - genetics
Phosphorylation - immunology
Protein Tyrosine Phosphatases - antagonists & inhibitors
Receptors, Antigen, T-Cell, gamma-delta - biosynthesis
Salmonella
T-Lymphocyte Subsets - enzymology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Tyrosine - metabolism
Up-Regulation - genetics
Up-Regulation - immunology
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Summary:Solute carrier 11A1 (SLC11A1) is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1) and the Bcg/Lsh/Ity locus. SLC11A1 was thought to be exclusively expressed in monocyte/macrophages and to have roles in phagosome maturation and cell activation. We characterized the expression of SLC11A1 in the majority of human and bovine γδ T cells and NK cells and in human CD3(+)CD45RO(+) T cells. Consistent with a role for iron-dependent inhibition of protein tyrosine phosphatases, SLC11A1(+) lymphocytes were more prone to activation and retained tyrosine phosphorylation. Transfection of SLC11A1 into a human γδ T cell-like line rendered the cells more prone to activation. Nonadherent splenocytes from wild-type mice expressed significantly greater IFN-γ compared with cells from Sv/129 (SLC11A1(-/-)) mice. Our data suggest that SLC11A1 has a heretofore unknown role in activation of a large subset of innate lymphocytes that are critical sources of IFN-γ. SLC11A1(+) animals have enhanced innate IFN-γ expression in response to Salmonella infection compared with SLC11A1(-) mice, which include commonly used inbred laboratory mice. Expression of SLC11A1 in innate lymphocytes and its role in augmenting their activation may account for inconsistencies in studies of innate lymphocytes in different animal models.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1200732