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PMID:25348153

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Citation

Wang, X, Sumida, H and Cyster, JG (2014) GPR18 is required for a normal CD8αα intestinal intraepithelial lymphocyte compartment. J. Exp. Med. 211:2351-9

Abstract

Intraepithelial lymphocytes (IELs) play an important role in maintaining the physiology of the small intestine. The majority of mouse IELs express CD8αα and are either γδ or αβ T cells. Although the development and homing of CD8αα IELs have been studied in some detail, the factors controlling their homeostasis and positioning are incompletely understood. Here we demonstrate that G protein-coupled receptor 18 (GPR18) is abundantly expressed in CD8αα IELs and that mice lacking this orphan receptor have reduced numbers of γδT IELs. Mixed bone marrow chimera experiments reveal a markedly reduced contribution of GPR18-deficient cells to the CD8αα IEL compartment and a reduction in the CD8αβ T cell subset. These defects could be rescued by transduction with a GPR18-expressing retrovirus. The GPR18-deficient γδT IELs that remained in mixed chimeras had elevated Thy1, and there were less granzyme B(+) and Vγ7(+) cells, indicating a greater reduction in effector-type cells. Flow cytometric analysis indicated GPR18 deficiency more strongly affected the CD8αα cells in the intraepithelial compared with the adjacent lamina propria compartment. These findings establish a requirement for GPR18 in CD8αα and CD8αβ IELs, and we suggest the receptor has a role in augmenting the accumulation of CD8 T cells in the intraepithelial versus lamina propria compartment.

Links

PubMed PMC4235638 Online version:10.1084/jem.20140646

Keywords

Animals; CD8 Antigens/immunology; CD8 Antigens/metabolism; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism; Epithelium/immunology; Epithelium/metabolism; Flow Cytometry; Gene Expression/immunology; Granzymes/immunology; Granzymes/metabolism; Intestine, Small/immunology; Intestine, Small/metabolism; Lymphocytes/immunology; Lymphocytes/metabolism; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence, Multiphoton; Receptors, Antigen, T-Cell, alpha-beta/immunology; Receptors, Antigen, T-Cell, alpha-beta/metabolism; Receptors, Antigen, T-Cell, gamma-delta/immunology; Receptors, Antigen, T-Cell, gamma-delta/metabolism; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/immunology; Receptors, G-Protein-Coupled/metabolism; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; Thy-1 Antigens/immunology; Thy-1 Antigens/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:S1PR1

involved_in

GO:0030595: leukocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CNR2

involved_in

GO:0030595: leukocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CXCR5

involved_in

GO:0030595: leukocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GP183

involved_in

GO:0030595: leukocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0002300: CD8-positive, alpha-beta intraepithelial T cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0002305: CD8-positive, gamma-delta intraepithelial T cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0002689: negative regulation of leukocyte chemotaxis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5708707

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0032720: negative regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5708707

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0002300: CD8-positive, alpha-beta intraepithelial T cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5708707

P

Seeded From UniProt

complete

MOUSE:GPR18

involved_in

GO:0002305: CD8-positive, gamma-delta intraepithelial T cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5708707

P

Seeded From UniProt

complete

MOUSE:MMP17

involved_in

GO:0042756: drinking behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3777020

P

Seeded From UniProt

complete

MOUSE:MMP17

involved_in

GO:0001822: kidney development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3777020

P

Seeded From UniProt

complete

MOUSE:CCR9

involved_in

GO:0002305: CD8-positive, gamma-delta intraepithelial T cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3654108

P

Seeded From UniProt

complete

MOUSE:CXCR5

acts_upstream_of_or_within

GO:0030595: leukocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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