Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner
The ubiquitously expressed tyrosine phosphatase Src homology region 2 domain-containing phosphatase-2 (SHP-2, encoded by Ptpn11) is required for constitutive cellular processes including proliferation, differentiation, and the regulation of immune responses. During development and maturation, subset...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01326/full |
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| author | S. M. Shahjahan Miah Chathuraka T. Jayasuriya Alexander I. Salter Emma C. Reilly Céline Fugere Wentian Yang Qian Chen Laurent Brossay |
| author_facet | S. M. Shahjahan Miah Chathuraka T. Jayasuriya Alexander I. Salter Emma C. Reilly Céline Fugere Wentian Yang Qian Chen Laurent Brossay |
| author_sort | S. M. Shahjahan Miah |
| collection | DOAJ |
| description | The ubiquitously expressed tyrosine phosphatase Src homology region 2 domain-containing phosphatase-2 (SHP-2, encoded by Ptpn11) is required for constitutive cellular processes including proliferation, differentiation, and the regulation of immune responses. During development and maturation, subsets of T cells express a variety of inhibitory receptors known to associate with phosphatases, which in turn, dephosphorylate key players of activating receptor signaling pathways. We hypothesized that SHP-2 deletion would have major effects on T cell development by altering the thresholds for activation, as well as positive and negative selection. Surprisingly, using mice conditionally deficient for SHP-2 in the T cell lineage, we show that the development of these lymphocytes is globally intact. In addition, our data demonstrate that SHP-2 absence does not compromise T cell effector functions, suggesting that SHP-2 is dispensable in these cells. Unexpectedly, in aging mice, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in wrist bones in a T cell-independent manner. These tumors resemble miniature cartilaginous growth plates and contain CD4-lineage positive chondrocyte-like cells. Altogether these results indicate that SHP-2 is a cartilage tumor suppressor during aging. |
| first_indexed | 2024-04-13T10:26:06Z |
| format | Article |
| id | doaj.art-50a394ed81284e4b95a06f6f2878920e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T10:26:06Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-50a394ed81284e4b95a06f6f2878920e2022-12-22T02:50:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01326309469Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent MannerS. M. Shahjahan Miah0Chathuraka T. Jayasuriya1Alexander I. Salter2Emma C. Reilly3Céline Fugere4Wentian Yang5Qian Chen6Laurent Brossay7Department of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Orthopaedics, Rhode Island Hospital and Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Orthopaedics, Rhode Island Hospital and Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Orthopaedics, Rhode Island Hospital and Brown University Alpert Medical School, Providence, RI, United StatesDepartment of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University Alpert Medical School, Providence, RI, United StatesThe ubiquitously expressed tyrosine phosphatase Src homology region 2 domain-containing phosphatase-2 (SHP-2, encoded by Ptpn11) is required for constitutive cellular processes including proliferation, differentiation, and the regulation of immune responses. During development and maturation, subsets of T cells express a variety of inhibitory receptors known to associate with phosphatases, which in turn, dephosphorylate key players of activating receptor signaling pathways. We hypothesized that SHP-2 deletion would have major effects on T cell development by altering the thresholds for activation, as well as positive and negative selection. Surprisingly, using mice conditionally deficient for SHP-2 in the T cell lineage, we show that the development of these lymphocytes is globally intact. In addition, our data demonstrate that SHP-2 absence does not compromise T cell effector functions, suggesting that SHP-2 is dispensable in these cells. Unexpectedly, in aging mice, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in wrist bones in a T cell-independent manner. These tumors resemble miniature cartilaginous growth plates and contain CD4-lineage positive chondrocyte-like cells. Altogether these results indicate that SHP-2 is a cartilage tumor suppressor during aging.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01326/fullSrc homology region 2 domain-containing phosphatase-2T cellsinvariant natural killer T cellscartilage tumorchondrocytes |
| spellingShingle | S. M. Shahjahan Miah Chathuraka T. Jayasuriya Alexander I. Salter Emma C. Reilly Céline Fugere Wentian Yang Qian Chen Laurent Brossay Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner Frontiers in Immunology Src homology region 2 domain-containing phosphatase-2 T cells invariant natural killer T cells cartilage tumor chondrocytes |
| title | Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner |
| title_full | Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner |
| title_fullStr | Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner |
| title_full_unstemmed | Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner |
| title_short | Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner |
| title_sort | ptpn11 deletion in cd4 cells does not affect t cell development and functions but causes cartilage tumors in a t cell independent manner |
| topic | Src homology region 2 domain-containing phosphatase-2 T cells invariant natural killer T cells cartilage tumor chondrocytes |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01326/full |
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