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Gene & Protein in Disease lncRNAs in trained immunity

specific functional states in immune cells. 34,35 Recent of group 1 ILCs, a category encompassing NK cells. These
findings indicate that the MALAT1 lncRNA is implicated in discoveries emphasize the integral role played by lncRNAs
the innate immune response. Elevated levels of MALAT1 in shaping the development and function of NK cells,
are observed in the invading cells of tolerized mice, and providing insights into the regulatory mechanisms within
MALAT1 overexpression favors the transition of DCs the immune system. 47
toward a tolerant phenotype. 36 The lncRNA GAS5 has emerged as a crucial regulator
2.3. lncRNAs’ impact on NK cell development and of the cytotoxic function of NK cells, particularly in the
activation context of hepatocellular carcinoma. The GAS5 exercises
control over the expression of IFN-γ in NK cells. On
NK cells are categorized as ILCs and, alongside monocytes, activation of GAS5, NK cells exhibit elevated levels
macrophages, and DCs, constitute the frontline defense of of IFN-γ. Conversely, when GAS5 is knocked down,
the innate immune system. Their primary functions involve the secretion of IFN-γ is significantly reduced. This
detecting and eliminating infected or abnormal cells, decrease in IFN-γ secretion is correlated with a decline
thereby playing pivotal roles in the immediate and rapid in NK cell cytotoxicity, diminished levels of CD107a+
responses of the innate immune system against diverse NK cells, and a reduction in apoptosis of HepG2 and
threats. NK cells operate autonomously of the antigen Huh7 cells. These findings underscore the pivotal role of
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processing and presentation pathways. Instead, they GAS5 in modulating the cytotoxic function of NK cells
carry out their functions by releasing pro-inflammatory and its potential impact on the immune response against
cytokines, such as interferon-gamma (IFN-γ), and hepatocellular carcinoma. 48
deploying cytotoxic granules containing perforin and
granzymes, leading to the lysis of target cells. This immediate 2.4. The function of Lnc-RNA in host-pathogen
and non-specific response is a characteristic feature of the interaction
innate immune system. Recent evidence further indicates Numerous lncRNA species play crucial roles in modulating
that innate immune memory can be transferred through immune responses against microbial components, thereby
progenitor and HSCs, highlighting the ability of specific significantly contributing to the coordination of the host’s
immune cells to retain a memory-like response to past defense mechanisms. One notable example is lincRNA-
encounters with pathogens, thereby contributing to a Cox2, located near the cyclooxygenase 2 (Cox2) gene.
more effective and rapid immune response on subsequent Initially discovered in murine DCs exposed to LPS, a
exposures. Building on this notion, NK cell memory bacterial cell wall component, the presence of lincRNA-
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has been acknowledged independently of T and B cells. Cox2 implies its potential role in orchestrating immune
Observations indicate that following exposure to cytokine responses to microbial stimuli. This is particularly relevant
combinations (e.g., IL-12, IL-15, and IL-18) or hapten within DCs, which are central players in coordinating
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sensitization, NK cells exhibit a heightened and more various aspects of the immune system. The expression
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robust response on encountering a previous challenge. This of the lincRNA‑Cox2 gene markedly increased when bone
underscores a form of memory-like behavior in the innate marrow-derived mouse macrophages (BMDMs) were
immune system, where NK cells display an enhanced stimulated with LPS or Pam3CSK4. Similarly, macrophages
capability to respond effectively to familiar threats. After infected with Listeria monocytogenes exhibited heightened
cytomegalovirus (CMV) infection, the activation of NK expression of lincRNA-Cox2. Another lncRNA, NEAT1,
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cells assumes a critical role in offering T cell-independent is implicated in regulating the immune response to
protection against reinfection. This protective mechanism microbial components. It serves as a crucial component of
involves the swift degranulation of cytotoxic granules the HEXIM1‑DNA‑PK-paraspeckle and ribonucleoprotein
and cytokine production, underscoring the remarkable complex (HDP-RNP). The knockdown of NEAT1 resulted
capacity of NK cells to orchestrate an accelerated and in the loss of IFN‑β mRNA expression over DNA (ISD)-
effective immune response when encountering a familiar mediated stimulation. Conversely, lncRNA-GM has
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pathogen for a second time. 46 been identified as a suppressor of viral replication and an
Emerging evidence strongly supports the participation enhancer of type I interferon (IFN-I) generation. In mice
of lncRNAs in both the development and activation of NK lacking the lncRNAs lncRNA-GM, there was an observed
cells. Specifically, lnc-CD56 has been identified as a key increase in sensitivity to viral infection, coupled with a
regulator influencing NK cell differentiation. In addition, reduction in interferon-I (IFN-I) production. Notably,
the lncRNA Rroid has been shown to exert regulatory LncRNA-GM was found to interact with glutathione
control over the expression of the transcriptional regulator S-transferase M1 (GSTM1), preventing GSTM1 from
ID2, thereby influencing the function and lineage identity engaging with the kinase TBK1. This interaction resulted

Volume 3 Issue 2 (2024) 6 doi: 10.36922/gpd.2791