The Immunological Epigenetic Landscape of the Human Life Trajectory
Adaptive immunity changes over an individual’s lifetime, maturing by adulthood and diminishing with old age. Epigenetic mechanisms involving DNA and histone methylation form the molecular basis of immunological memory during lymphocyte development. Monocytes alter their function to convey immune tol...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2894 |
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| author | Iva Juříčková Michael Hudec Felix Votava Jan Vosáhlo Saak Victor Ovsepian Marie Černá Valerie Bríd O’Leary |
| author_facet | Iva Juříčková Michael Hudec Felix Votava Jan Vosáhlo Saak Victor Ovsepian Marie Černá Valerie Bríd O’Leary |
| author_sort | Iva Juříčková |
| collection | DOAJ |
| description | Adaptive immunity changes over an individual’s lifetime, maturing by adulthood and diminishing with old age. Epigenetic mechanisms involving DNA and histone methylation form the molecular basis of immunological memory during lymphocyte development. Monocytes alter their function to convey immune tolerance, yet the epigenetic influences at play remain to be fully understood in the context of lifespan. This study of a healthy genetically homogenous cohort of children, adults and seniors sought to decipher the epigenetic dynamics in B-lymphocytes and monocytes. Variable global cytosine methylation within retro-transposable <i>LINE-1</i> repeats was noted in monocytes compared to B-lymphocytes across age groups. The expression of the human leukocyte antigen (<i>HLA</i>)<i>-DQ alpha chain</i> gene <i>HLA-DQA1*01</i> revealed significantly reduced levels in monocytes in all ages relative to B-lymphocytes, as well as between lifespan groups. High melting point analysis and bisulfite sequencing of the <i>HLA-DQA1*01</i> promoter in monocytes highlighted variable cytosine methylation in children and seniors but greater stability at this locus in adults. Further epigenetic evaluation revealed higher histone lysine 27 trimethylation in monocytes from this adult group. Chromatin immunoprecipitation and RNA pulldown demonstrated association with a novel lncRNA <i>TINA</i> with structurally conserved similarities to the previously recognized epigenetic modifier <i>PARTICLE</i>. Seeking to interpret the epigenetic immunological landscape across three representative age groups, this study focused on <i>HLA-DQA1*01</i> to expose cytosine and histone methylation alterations and their association with the non-coding transcriptome. Such insights unveil previously unknown complex epigenetic layers, orchestrating the strength and weakening of adaptive immunity with the progression of life. |
| first_indexed | 2024-03-09T18:27:27Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:27Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7a0f0abbc0074fb7be87fcb382f211902023-11-24T07:45:49ZengMDPI AGBiomedicines2227-90592022-11-011011289410.3390/biomedicines10112894The Immunological Epigenetic Landscape of the Human Life TrajectoryIva Juříčková0Michael Hudec1Felix Votava2Jan Vosáhlo3Saak Victor Ovsepian4Marie Černá5Valerie Bríd O’Leary6Department of Medical Genetics, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicDepartment of Medical Genetics, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicDepartment of Children and Adolescents, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicDepartment of Children and Adolescents, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicFaculty of Engineering and Science, University of Greenwich London, Chatham Maritime, Kent ME4 4TB, UKDepartment of Medical Genetics, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicDepartment of Medical Genetics, Third Faculty of Medicine, Charles University, Vinohrady, 10000 Prague, Czech RepublicAdaptive immunity changes over an individual’s lifetime, maturing by adulthood and diminishing with old age. Epigenetic mechanisms involving DNA and histone methylation form the molecular basis of immunological memory during lymphocyte development. Monocytes alter their function to convey immune tolerance, yet the epigenetic influences at play remain to be fully understood in the context of lifespan. This study of a healthy genetically homogenous cohort of children, adults and seniors sought to decipher the epigenetic dynamics in B-lymphocytes and monocytes. Variable global cytosine methylation within retro-transposable <i>LINE-1</i> repeats was noted in monocytes compared to B-lymphocytes across age groups. The expression of the human leukocyte antigen (<i>HLA</i>)<i>-DQ alpha chain</i> gene <i>HLA-DQA1*01</i> revealed significantly reduced levels in monocytes in all ages relative to B-lymphocytes, as well as between lifespan groups. High melting point analysis and bisulfite sequencing of the <i>HLA-DQA1*01</i> promoter in monocytes highlighted variable cytosine methylation in children and seniors but greater stability at this locus in adults. Further epigenetic evaluation revealed higher histone lysine 27 trimethylation in monocytes from this adult group. Chromatin immunoprecipitation and RNA pulldown demonstrated association with a novel lncRNA <i>TINA</i> with structurally conserved similarities to the previously recognized epigenetic modifier <i>PARTICLE</i>. Seeking to interpret the epigenetic immunological landscape across three representative age groups, this study focused on <i>HLA-DQA1*01</i> to expose cytosine and histone methylation alterations and their association with the non-coding transcriptome. Such insights unveil previously unknown complex epigenetic layers, orchestrating the strength and weakening of adaptive immunity with the progression of life.https://www.mdpi.com/2227-9059/10/11/2894<i>HLA</i>histonemethylation<i>TINA</i><i>PARTICLE</i>long non-coding RNA |
| spellingShingle | Iva Juříčková Michael Hudec Felix Votava Jan Vosáhlo Saak Victor Ovsepian Marie Černá Valerie Bríd O’Leary The Immunological Epigenetic Landscape of the Human Life Trajectory Biomedicines <i>HLA</i> histone methylation <i>TINA</i> <i>PARTICLE</i> long non-coding RNA |
| title | The Immunological Epigenetic Landscape of the Human Life Trajectory |
| title_full | The Immunological Epigenetic Landscape of the Human Life Trajectory |
| title_fullStr | The Immunological Epigenetic Landscape of the Human Life Trajectory |
| title_full_unstemmed | The Immunological Epigenetic Landscape of the Human Life Trajectory |
| title_short | The Immunological Epigenetic Landscape of the Human Life Trajectory |
| title_sort | immunological epigenetic landscape of the human life trajectory |
| topic | <i>HLA</i> histone methylation <i>TINA</i> <i>PARTICLE</i> long non-coding RNA |
| url | https://www.mdpi.com/2227-9059/10/11/2894 |
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