ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production
SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary su...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00549/full |
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| author | Etienne Masle-Farquhar Etienne Masle-Farquhar Angelika Bröer Mehmet Yabas Anselm Enders Stefan Bröer |
| author_facet | Etienne Masle-Farquhar Etienne Masle-Farquhar Angelika Bröer Mehmet Yabas Anselm Enders Stefan Bröer |
| author_sort | Etienne Masle-Farquhar |
| collection | DOAJ |
| description | SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients. |
| first_indexed | 2024-12-23T19:51:06Z |
| format | Article |
| id | doaj.art-49b10148616c48af908c7ec0b1db5af4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T19:51:06Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-49b10148616c48af908c7ec0b1db5af42022-12-21T17:33:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-05-01810.3389/fimmu.2017.00549248020ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody ProductionEtienne Masle-Farquhar0Etienne Masle-Farquhar1Angelika Bröer2Mehmet Yabas3Anselm Enders4Stefan Bröer5Research School of Biology, The Australian National University, Canberra, ACT, AustraliaDepartment of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, AustraliaResearch School of Biology, The Australian National University, Canberra, ACT, AustraliaResearch School of Biology, The Australian National University, Canberra, ACT, AustraliaDepartment of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, AustraliaResearch School of Biology, The Australian National University, Canberra, ACT, AustraliaSLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00549/fullSLC1A5glutamineB cellsglutaminolysisASCT2glutamine uptake |
| spellingShingle | Etienne Masle-Farquhar Etienne Masle-Farquhar Angelika Bröer Mehmet Yabas Anselm Enders Stefan Bröer ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production Frontiers in Immunology SLC1A5 glutamine B cells glutaminolysis ASCT2 glutamine uptake |
| title | ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production |
| title_full | ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production |
| title_fullStr | ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production |
| title_full_unstemmed | ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production |
| title_short | ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production |
| title_sort | asct2 slc1a5 deficient mice have normal b cell development proliferation and antibody production |
| topic | SLC1A5 glutamine B cells glutaminolysis ASCT2 glutamine uptake |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00549/full |
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