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Gene & Protein in Disease lncRNAs in trained immunity

in the attenuation of GSTM1-mediated S-glutathionylation may demonstrate memory-like characteristics following
of TBK1. The subsequent decrease in S-glutathionylation LPS induction. Recent studies have unveiled that trained
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led to heightened TBK1 activity, thereby amplifying the immunity responses are not exclusive to macrophages;
downstream production of antiviral mediators. These monocytes have also been proven to exhibit such responses
findings highlight the regulatory role of lncRNA-GM in after infection by parasitic pathoigens and viral agent.
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the antiviral immune response by modulating the activity Monocytes typically have a short half-life in circulation,
of key signaling molecules integral to the innate immune lasting up to 1 day. However, it is intriguing to note that
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system. 52 trained monocytes have been identified in the bloodstream
of individuals vaccinated with BCG for at least 3-month
2.5. Epigenetically modified lncRNAs: their impact post-vaccination. This observation suggests that the
on immunity reprogramming leading to trained immunity occurs at the
Epigenetic alterations on lncRNAs play a crucial role progenitor cell level in the bone marrow. The prolonged
in modulating their expression levels and functional presence of trained monocytes in circulation underscores
outcomes. Notably, the hypomethylation of MALAT1 the enduring impact of BCG vaccination on the immune
has been linked to increased expression, correlating with system, emphasizing the potential establishment of innate
elevated production of inflammatory cytokines. Similarly, immune memory at the level of progenitor cells in the
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the presence of H3K27 acetylation in the promoter bone marrow. 65
region of NEAT1 facilitates inflammasome assembly and Although the mechanism of trained immunity is
activation, underscoring the intricate regulatory influence still being unraveled, there is compelling evidence
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of epigenetic modifications on immune responses. 54 indicating that epigenetic reprogramming, including
2.6. lncRNAs’ confirmations and implications in histone modification, DNA methylation, and ncRNA,
immunity plays a substantial role in this process (Figure 3). Histone
alterations and chromatin reconfiguration have been
LncRNAs, although unable to encode proteins, assume identified as important processes in the development
distinct structural configurations that facilitate interactions of learned (trained) immunity. H3K27Ac, H3K4me1/2,
with various molecules. For example, the presence of H3K4me3, histone H3.3, and H3K36me3 have all
N6-methyladenosine modifications within lncRNA been found to be upregulated by reinfection. 66-68 When
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hairpins predisposes them to protein binding. Consider challenged by the human CMV (HCMV), NK cells
MALAT1, which undergoes reversible methylation at displayed trained immunity through DNA methylation. 69
position A2577, thereby promoting HNRNPC protein
binding. Furthermore, m6A modifications stabilize 3.1. lncRNAs: orchestrators of epigenetic regulation
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MALAT1 and activate the NF-κB pathway. The in trained immunity
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incorporation of multivalent structural motifs and long- Beyond immune cell development, lncRNAs play a critical
stem structures is crucial for lnc-Lsm3b’s interaction with role in epigenetically modulating the human genome.
the innate RNA sensor RIG-I, leading to inhibition. These Operating through direct interactions with histone
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findings collectively suggest a significant role for lncRNA writers, readers, and erasers, lncRNAs significantly impact
conformation in immune responses. chromatin structure and gene expression by influencing

3. lncRNAs’ function in trained immunity histone modifications. The intricate involvement of
lncRNAs in epigenetic processes underscores their
The concept of “trained immunity” was introduced by multifaceted role in shaping the epigenome and
Netea et al. to elucidate the phenomenon wherein innate influencing diverse cellular functions. Indeed, lncRNAs
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immune cells, notably macrophages, monocytes, and NK play a significant role in human diseases, including cancer,
cells, display heightened reactivity on reencountering inflammation, and schizophrenia, by interacting with
infections, even in the absence of adaptive immunity. This epigenetic factors. In the context of glioma, the lncRNA
enhanced immune response is linked to a notable shift MIR155HG has been observed to undergo epigenetic
in cellular metabolism and epigenetic reprogramming, activation. This activation is mediated by promoter
particularly at the level of histone modifications. 18,59 hypomethylation and involves the transcription factor SP1.
Epigenetic reprogramming induced alterations in Importantly, the epigenetic changes in MIR155HG have
gene expression without affecting the underlying DNA been correlated with immune infiltration in glioma. This
sequences. Notably, these modifications exhibited a lasting suggests a link between epigenetic regulation of specific
impact that could endure across numerous generations. lncRNAs and the modulation of immune responses in the
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Furthermore, studies have indicated that macrophages context of certain diseases, such as glioma. The study by
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Volume 3 Issue 2 (2024) 7 doi: 10.36922/gpd.2791