Simon Steen-Andersen

[Simon Steen-Andersen @s_steenandersen]

@AaronGoodman33 Could JMJD3 be interesting to elucidate as epigentic control of CD1d? During DC-T cell crosstalk, IL-2-induced pSTAT5 activates the transcriptional machinery of IL12RB2, thereby initiating JMJD3, which regulates chromatin decondensation in a functional cooperation with T-bet?

[Simon Steen-Andersen @s_steenandersen]

@nedigga3 @davidasinclair EZH2 inhibitors, maybe?

[Simon Steen-Andersen @s_steenandersen]

@davidasinclair -, it seems important to elucidate the role of IL12RB2 as an interface for molecular and cellular signaling events acting in trans in aging, self renewal and autoimmune & cancerous proliferation,- in addition to understanding its role in the heterodimeric IL-12 receptor complex.

[Simon Steen-Andersen @s_steenandersen]

@davidasinclair Given that JMJD3 has been found to play a non-redundant role in stemness & differentiation, and that the transcriptional machinery of IL12RB2 regulates major epigenetic events during proliferation & differentiation in a functional cooperation with CD25/STAT5, T-bet & JMJD3 - ...

[Simon Steen-Andersen @s_steenandersen]

@HealthSci_AI @davidasinclair Interesting question! In T cells, does there exist a functional interplay between TET2 & enhancers/superenhancers, as TET2 gets recruited to lineage specific TFs, & does demethylation via IL12RB2-dependent JMJD3 upon IL-2/pSTAT5 activation plays a role, during DC/CD4+ crosstalk?

[Simon Steen-Andersen @s_steenandersen]

@davidasinclair Interesting research! Is your lab also interested in TET2 in T cells,- in the possible interplay between Tet2 & superenhancers, as TET2 gets recruited to lineage specific TFs & in elucidating if demethylation via IL12RB2-dependent JMJD3 upon IL-2/pSTAT5 activation plays a role?

[Simon Steen-Andersen @s_steenandersen]

@RuxandraTeslo The gain of methylation on PRC2 target genes might derive from deficient STAT5induced IL12RB2mRNA processing during self-renewal with insufficient JMJD3-mediated decondensation of PRC2-genes while other cell types express increased type 1 IFN, driving constitutive proliferation

[Simon Steen-Andersen @s_steenandersen]

@RuxandraTeslo Although aging follows an individual trajectory, the complex process of aging involves upregulation of the innate & downregulation of the adaptive immunity as well as a decline in CD8+T numbers & function, including increased H3K27me3 on IL12RB2. Is neuronal PRC2 JMJD3-mediated?

[Simon Steen-Andersen @s_steenandersen]

@iannaconelab ...the last step required for high level IL12p70-induced IFNγ derived from fully differentiated TH1 cells which are essential for macrophage activation & mature granuloma formation in a setting with infection caused by intracellular bacteria but not by LCMV with rapid clearance?

[Simon Steen-Andersen @s_steenandersen]

@iannaconelab Since not all viruses are capable of inducing unconjugated ISG15, their differential polarization patterns might depend on DC-derived ISG15-induced IFN-γ and the kinetics of IL-12p40 vs IL-12p35 induction, with TPL-2-induced p38 mapk upon IL-2-induced pSTAT5/IL12RB2 being ...

[Simon Steen-Andersen @s_steenandersen]

@globalimmuno @shenorr Of note, the downregulated genes in CD8 T cells from old donors have been shown to exhibit low expression of IL12RB2. Given the ability of early IL12RB2 signaling during DC-T cell crosstalk to influence JMJD3, p38 mapk & IL12A, its secondary signals acting in trans seems relevant

[Simon Steen-Andersen @s_steenandersen]

@globalimmuno @shenorr #immunotalks The potential role for IL12RB2 as a bridge between innate and adaptive immunity in Mtb infection might also make the methylation status of IL12RB2 an intersting marker for aging-related changes, in alignment with the upregulation of innate immunity induced by aging.