EOMES

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Eomesodermin homolog (T-box brain protein 2) (T-brain-2) (TBR-2) [TBR2]

Publications[править]

Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort.

How the measurement of aging biomarkers in peripheral blood T-lymphocytes (PBTLs) is influenced by cell composition is unclear. Here, we collected peripheral blood and isolated CD3 PBTLs from 117 healthy couples between the ages of 21 and 72. Each sample was profiled for Horvath epigenetic clock (DNAm), p16INK4a expression, cytomegalovirus (CMV) seropositivity and 74 mRNA markers of PBTL subtype, differentiation, immune checkpoints, and cytokine production. Correlations between individual aging biomarkers (DNAm or p16INK4a) and PBTL mRNAs were corrected for chronological age, sex, and couple. DNAm measurements correlated with CMV seropositivity as well as PBTL mRNAs indicative of effector function (CD8A, EOMES, TBX21, GZMB), poor proliferative capacity (KLRG1, CD57), differentiation (CD45RO, CD45RA), and immune checkpoints (PDCD1, TIGIT, LAG3, CD160, CD244). In contrast, only three PBTL mRNAs, CD28, CD244, and p14ARF, showed a significant association with p16INK4a. p16INK4a expression also showed a weaker association with immunosenescent PBTL subsets than DNAm in flow cytometry analyses. These data suggest that PBTL composition has a greater influence on DNAm than p16INK4a and link accelerated epigenetic aging to immunosenescent phenotypes.


Keywords

  • Aging biomarker
  • CMV
  • Horvath clock
  • Senescence
  • T cell


Eomesodermin Expression in CD4 T Cells Restricts Peripheral Foxp3 Induction.

CD4( ) T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3( ) regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4( ) T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4( ) T lymphocytes. We find that Eomes is readily expressed in activated CD4( ) Th1 T cells in vivo. Eomes( ) CD4( ) T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4( ) T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3( ) cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4( ) T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4( ) T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4( ) T cells. This enhanced capacity of Eomes-deficient CD4( ) T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3( ) cells. Our data identify a novel role for Eomes in CD4( ) T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.

MeSH Terms

  • Aging
  • Animals
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental
  • Forkhead Transcription Factors
  • Interferon-gamma
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Box Domain Proteins
  • T-Lymphocytes, Regulatory
  • Th1 Cells
  • Th17 Cells
  • Th2 Cells