Limits...
The lysophosphatidylserine receptor GPR174 constrains regulatory T cell development and function.

Barnes MJ, Li CM, Xu Y, An J, Huang Y, Cyster JG - J. Exp. Med. (2015)

Bottom Line: In vivo, LysoPS was detected in lymphoid organ and spinal cord tissues and was abundant in the colon.This study provides evidence that a bioactive lipid, LysoPS, negatively influences T reg cell accumulation and activity through GPR174.As such, GPR174 antagonists might have therapeutic potential for promoting immune regulation in the context of autoimmune disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.

Show MeSH

Related in: MedlinePlus

LysoPS is abundant in lymphoid tissues and can be generated by various immune cell types. (A) Concentrations of 16:0, 18:0, and 18:1 LysoPS were measured under homeostatic conditions in the indicated tissues using LC-MS/MS. (B) Transcript levels of LysoPS synthetic and metabolic enzymes were measured by quantitative RT-PCR in the indicated cell populations and tissues. In both panels, each dot represents a separate mouse; n = 3–5. (A and B) Horizontal lines indicate the mean.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4493414&req=5

fig4: LysoPS is abundant in lymphoid tissues and can be generated by various immune cell types. (A) Concentrations of 16:0, 18:0, and 18:1 LysoPS were measured under homeostatic conditions in the indicated tissues using LC-MS/MS. (B) Transcript levels of LysoPS synthetic and metabolic enzymes were measured by quantitative RT-PCR in the indicated cell populations and tissues. In both panels, each dot represents a separate mouse; n = 3–5. (A and B) Horizontal lines indicate the mean.

Mentions: Given the effects of LysoPS on T cells, we next investigated whether LysoPS was present in lymphoid organs under homeostatic conditions. Previously, LysoPS concentrations were reported for selected tissues, including the liver (Blankman et al., 2013), in which 18:0, 18:1, and 16:0 LysoPS were among the most common isoforms. We developed a liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) procedure for measuring LysoPS and detected concentrations of the 16:0, 18:0, and 18:1 isoforms in the liver that were similar to those measured by Blankman et al. (2013; Fig. 4 A). The thymus, spleen, and LNs each contained abundant LysoPS, with the 18:0 isoform being the most common, followed by 18:1 and 16:0 (Fig. 4 A). Although this analysis did not permit the extra- and intracellular pools of LysoPS to be distinguished, it is notable that a concentration of 1 µg/g corresponds to ∼2 µM LysoPS. Plasma contained much lower concentrations of all three LysoPS isoforms that were below the limit of detection for our assay (not depicted). We also analyzed LysoPS concentrations in two common sites of immunopathology. Spinal cord tissues exhibited slightly lower 18:0 and 16:0 LysoPS concentrations compared with lymphoid tissues but contained almost an order of magnitude more 18:1 LysoPS (Fig. 4 A). Colon tissues contained an order of magnitude more 18:0 LysoPS compared with any other tissue measured, in addition to high levels of 18:1 and 16:0 LysoPS (Fig. 4 A).


The lysophosphatidylserine receptor GPR174 constrains regulatory T cell development and function.

Barnes MJ, Li CM, Xu Y, An J, Huang Y, Cyster JG - J. Exp. Med. (2015)

LysoPS is abundant in lymphoid tissues and can be generated by various immune cell types. (A) Concentrations of 16:0, 18:0, and 18:1 LysoPS were measured under homeostatic conditions in the indicated tissues using LC-MS/MS. (B) Transcript levels of LysoPS synthetic and metabolic enzymes were measured by quantitative RT-PCR in the indicated cell populations and tissues. In both panels, each dot represents a separate mouse; n = 3–5. (A and B) Horizontal lines indicate the mean.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493414&req=5

fig4: LysoPS is abundant in lymphoid tissues and can be generated by various immune cell types. (A) Concentrations of 16:0, 18:0, and 18:1 LysoPS were measured under homeostatic conditions in the indicated tissues using LC-MS/MS. (B) Transcript levels of LysoPS synthetic and metabolic enzymes were measured by quantitative RT-PCR in the indicated cell populations and tissues. In both panels, each dot represents a separate mouse; n = 3–5. (A and B) Horizontal lines indicate the mean.
Mentions: Given the effects of LysoPS on T cells, we next investigated whether LysoPS was present in lymphoid organs under homeostatic conditions. Previously, LysoPS concentrations were reported for selected tissues, including the liver (Blankman et al., 2013), in which 18:0, 18:1, and 16:0 LysoPS were among the most common isoforms. We developed a liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) procedure for measuring LysoPS and detected concentrations of the 16:0, 18:0, and 18:1 isoforms in the liver that were similar to those measured by Blankman et al. (2013; Fig. 4 A). The thymus, spleen, and LNs each contained abundant LysoPS, with the 18:0 isoform being the most common, followed by 18:1 and 16:0 (Fig. 4 A). Although this analysis did not permit the extra- and intracellular pools of LysoPS to be distinguished, it is notable that a concentration of 1 µg/g corresponds to ∼2 µM LysoPS. Plasma contained much lower concentrations of all three LysoPS isoforms that were below the limit of detection for our assay (not depicted). We also analyzed LysoPS concentrations in two common sites of immunopathology. Spinal cord tissues exhibited slightly lower 18:0 and 16:0 LysoPS concentrations compared with lymphoid tissues but contained almost an order of magnitude more 18:1 LysoPS (Fig. 4 A). Colon tissues contained an order of magnitude more 18:0 LysoPS compared with any other tissue measured, in addition to high levels of 18:1 and 16:0 LysoPS (Fig. 4 A).

Bottom Line: In vivo, LysoPS was detected in lymphoid organ and spinal cord tissues and was abundant in the colon.This study provides evidence that a bioactive lipid, LysoPS, negatively influences T reg cell accumulation and activity through GPR174.As such, GPR174 antagonists might have therapeutic potential for promoting immune regulation in the context of autoimmune disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.

Show MeSH
Related in: MedlinePlus