Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases
Co-signaling molecules include co-stimulatory and co-inhibitory molecules and play important roles in modulating immune responses. The roles of co-signaling molecules in autoimmune diseases have not been clearly defined. We assessed the expressions of co-stimulatory and co-inhibitory molecules in au...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00261/full |
| _version_ | 1819174390400548864 |
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| author | Weiwei He Bin Wang Qian Li Qiuming Yao Xi Jia Ronghua Song Sheli Li Jin-an Zhang |
| author_facet | Weiwei He Bin Wang Qian Li Qiuming Yao Xi Jia Ronghua Song Sheli Li Jin-an Zhang |
| author_sort | Weiwei He |
| collection | DOAJ |
| description | Co-signaling molecules include co-stimulatory and co-inhibitory molecules and play important roles in modulating immune responses. The roles of co-signaling molecules in autoimmune diseases have not been clearly defined. We assessed the expressions of co-stimulatory and co-inhibitory molecules in autoimmune diseases through a bioinformatics-based study. By using datasets of whole-genome transcriptome, the expressions of 54 co-stimulatory or co-inhibitory genes in common autoimmune diseases were analyzed using Robust rank aggregation (RRA) method. Nineteen array datasets and 6 RNA-seq datasets were included in the RRA discovery study and RRA validation study, respectively. Significant genes were further validated in several autoimmune diseases including Graves' disease (GD). RRA discovery study suggested that CD160 was the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-12), followed by CD58 (Adjusted P = 5.7E-06) and CD244 (Adjusted P = 9.5E-05). RRA validation study also identified CD160 as the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-09). We further found that the aberrant expression of CD160 was statistically significant in multiple autoimmune diseases including GD (P < 0.05), and CD160 had a moderate role in diagnosing those autoimmune diseases. Flow cytometry confirmed that CD160 was differentially expressed on the surface of CD8+ T cells between GD patients and healthy controls (P = 0.002), which proved the aberrant expression of CD160 in GD at the protein level. This study suggests that CD160 is the most significant co-signaling gene aberrantly expressed in autoimmune diseases. Treatment strategy targeting CD160-related pathway may be promising for the therapy of autoimmune diseases. |
| first_indexed | 2024-12-22T20:38:13Z |
| format | Article |
| id | doaj.art-8048268b81e64190957e7fcda89eb2f7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:38:13Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8048268b81e64190957e7fcda89eb2f72022-12-21T18:13:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00261428263Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune DiseasesWeiwei He0Bin Wang1Qian Li2Qiuming Yao3Xi Jia4Ronghua Song5Sheli Li6Jin-an Zhang7Department of Endocrinology, Affiliated Hospital of Yanan Medical University, Yanan, ChinaDepartment of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, ChinaDepartment of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, ChinaDepartment of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, ChinaDepartment of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, ChinaDepartment of Endocrinology and Rheumatology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology, Affiliated Hospital of Yanan Medical University, Yanan, ChinaDepartment of Endocrinology and Rheumatology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaCo-signaling molecules include co-stimulatory and co-inhibitory molecules and play important roles in modulating immune responses. The roles of co-signaling molecules in autoimmune diseases have not been clearly defined. We assessed the expressions of co-stimulatory and co-inhibitory molecules in autoimmune diseases through a bioinformatics-based study. By using datasets of whole-genome transcriptome, the expressions of 54 co-stimulatory or co-inhibitory genes in common autoimmune diseases were analyzed using Robust rank aggregation (RRA) method. Nineteen array datasets and 6 RNA-seq datasets were included in the RRA discovery study and RRA validation study, respectively. Significant genes were further validated in several autoimmune diseases including Graves' disease (GD). RRA discovery study suggested that CD160 was the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-12), followed by CD58 (Adjusted P = 5.7E-06) and CD244 (Adjusted P = 9.5E-05). RRA validation study also identified CD160 as the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-09). We further found that the aberrant expression of CD160 was statistically significant in multiple autoimmune diseases including GD (P < 0.05), and CD160 had a moderate role in diagnosing those autoimmune diseases. Flow cytometry confirmed that CD160 was differentially expressed on the surface of CD8+ T cells between GD patients and healthy controls (P = 0.002), which proved the aberrant expression of CD160 in GD at the protein level. This study suggests that CD160 is the most significant co-signaling gene aberrantly expressed in autoimmune diseases. Treatment strategy targeting CD160-related pathway may be promising for the therapy of autoimmune diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.00261/fullautoimmune diseasesco-stimulatory moleculesco-inhibitory moleculesGraves' diseaseCD160 |
| spellingShingle | Weiwei He Bin Wang Qian Li Qiuming Yao Xi Jia Ronghua Song Sheli Li Jin-an Zhang Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases Frontiers in Immunology autoimmune diseases co-stimulatory molecules co-inhibitory molecules Graves' disease CD160 |
| title | Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases |
| title_full | Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases |
| title_fullStr | Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases |
| title_full_unstemmed | Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases |
| title_short | Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases |
| title_sort | aberrant expressions of co stimulatory and co inhibitory molecules in autoimmune diseases |
| topic | autoimmune diseases co-stimulatory molecules co-inhibitory molecules Graves' disease CD160 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00261/full |
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