PMID- 36428462
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 11
DP  - 2022 Nov 11
TI  - The Immunological Epigenetic Landscape of the Human Life Trajectory.
LID - 10.3390/biomedicines10112894 [doi]
LID - 2894
AB  - 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 
      LINE-1 repeats was noted in monocytes compared to B-lymphocytes across age 
      groups. The expression of the human leukocyte antigen (HLA)-DQ alpha chain gene 
      HLA-DQA1*01 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 HLA-DQA1*01 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 
      TINA with structurally conserved similarities to the previously recognized 
      epigenetic modifier PARTICLE. Seeking to interpret the epigenetic immunological 
      landscape across three representative age groups, this study focused on 
      HLA-DQA1*01 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.
FAU - Jurickova, Iva
AU  - Jurickova I
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Vinohrady, 10000 Prague, Czech Republic.
FAU - Hudec, Michael
AU  - Hudec M
AUID- ORCID: 0000-0002-6593-9911
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Vinohrady, 10000 Prague, Czech Republic.
FAU - Votava, Felix
AU  - Votava F
AD  - Department of Children and Adolescents, Third Faculty of Medicine, Charles 
      University, Vinohrady, 10000 Prague, Czech Republic.
AD  - Kralovske Vinohrady University Hospital, Vinohrady, 10034 Prague, Czech Republic.
FAU - Vosahlo, Jan
AU  - Vosahlo J
AD  - Department of Children and Adolescents, Third Faculty of Medicine, Charles 
      University, Vinohrady, 10000 Prague, Czech Republic.
AD  - Kralovske Vinohrady University Hospital, Vinohrady, 10034 Prague, Czech Republic.
FAU - Ovsepian, Saak Victor
AU  - Ovsepian SV
AD  - Faculty of Engineering and Science, University of Greenwich London, Chatham 
      Maritime, Kent ME4 4TB, UK.
FAU - Cerna, Marie
AU  - Cerna M
AUID- ORCID: 0000-0002-1208-5588
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Vinohrady, 10000 Prague, Czech Republic.
FAU - O'Leary, Valerie Brid
AU  - O'Leary VB
AUID- ORCID: 0000-0003-1171-9830
AD  - Department of Medical Genetics, Third Faculty of Medicine, Charles University, 
      Vinohrady, 10000 Prague, Czech Republic.
LA  - eng
GR  - 207036/COOPERATIO: the scientific project 'Medical Diagnostics and Basic Medical 
      Sciences' (the field 'Medical Genetics')/
GR  - 260531/SVV/2020-2022/Charles University/
PT  - Journal Article
DEP - 20221111
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9687906
OTO - NOTNLM
OT  - ChIP
OT  - HLA
OT  - PARTICLE
OT  - TINA
OT  - histone
OT  - long non-coding RNA
OT  - methylation
COIS- The authors declare no conflict of interest.
EDAT- 2022/11/27 06:00
MHDA- 2022/11/27 06:01
PMCR- 2022/11/11
CRDT- 2022/11/26 01:03
PHST- 2022/10/07 00:00 [received]
PHST- 2022/10/26 00:00 [revised]
PHST- 2022/11/08 00:00 [accepted]
PHST- 2022/11/26 01:03 [entrez]
PHST- 2022/11/27 06:00 [pubmed]
PHST- 2022/11/27 06:01 [medline]
PHST- 2022/11/11 00:00 [pmc-release]
AID - biomedicines10112894 [pii]
AID - biomedicines-10-02894 [pii]
AID - 10.3390/biomedicines10112894 [doi]
PST - epublish
SO  - Biomedicines. 2022 Nov 11;10(11):2894. doi: 10.3390/biomedicines10112894.