We have modeled the impact of glucocorticoids on immune function by treatment of an NK cell line with dexamethasone, which reduces natural killer cell function though epigenetic modification of effector gene regulatory region accessibility.
This is surprising, as the C-terminal region of AnkB of strain Philadelphia contains a eukaryotic prenylation C AAX motif mediating posttranslational modification of effector proteins, important for intracellular replication of L. pneumophila.
For example, modification of immune effector engagement has improved pharmacokinetic profiles, and conjugating cytotoxic agents to mAbs has enhanced targeted therapeutic delivery to tumors.
In addition, it points to modifications of Tfh effector molecules or Tfh subset balance as future therapeutic targets in RA.
These structural modifications enhance docking of effector proteins whose recruitment induces the activation of downstream signal transduction pathways, including Mitogen-Activated Protein Kinase (MAPK) and Phospatidylinositol-3 Kinase (PI-3K) pathways [ 7, 13, 14].
Finally, MGCs denoting histone proteins (IPR005819, IPR009072), deacetylase (IPR000286, IPR003000) and acetyltransferase (IPR015418) enzymes confirm the importance of chromatin remodelling and histone modifications in the regulated transcription of effector genes.
Differentiation of T cells is characterized by a number of phenotypic and functional alterations, such as changes in their migratory capacities, modification to their lifespan, and secretion of effector cytokines (e.g. IL-4 and IFN-γ).
SC1 sought to address whether changes in gene expression are sufficiently informative to infer the molecular modifications observed upstream, in particular, the phosphorylation status of effector proteins.
[Editors' note: this article was originally rejected after discussions between the reviewers, but the authors were invited to resubmit after an appeal against the decision.] Thank you for choosing to send your work entitled "Epigenetic modification of the PD-1 (promoterromoter in effector CD4+ T cells tolerized by peptide immunotherapy" for consideration at eLife.
Given the availability and decreasing cost of NGS technology, effectors and effector-triggered modifications can be dissected one by one to unveil the mechanisms of effector triggered susceptibility (ETS).
This is in contrast to tail modifications that play a mainly indirect role in chromatin regulation through recruitment of effector proteins.
