Page 10 - GPD-3-2

Gene & Protein in Disease lncRNAs in trained immunity

types of blood cells. This includes cells belonging to both and presenting antigens, facilitating wound repair, and
myeloid and lymphoid lineages. Within the lymphoid releasing both pro- and anti-inflammatory mediators. In
lineage, HSCs can give rise to T cells, B cells, and NK cells. the intricate landscape of macrophage development and
On the other hand, myeloid lineage differentiation leads polarization, a multitude of lncRNAs have been recognized
to the formation of diverse cell types, such as monocytes, for their substantial roles. One noteworthy lncRNA in this
macrophages, erythrocytes, basophils, neutrophils, context is lncMorrbid, a conserved element observed in
eosinophils, and megakaryocytes. The differentiation species such as humans and mice. Initially identified in
potential of HSCs plays a pivotal role in maintaining murine myeloid cells, including eosinophils, neutrophils,
the balance and functionality of the entire blood cell and Ly6C hi-monocytes, lncMorrbid assumes a critical
repertoire. DCs have a heterogeneous hematopoietic role in regulating myeloid cell lifespan by modulating the
lineage and can be generated from both lymphoid and pro-apoptotic gene Bim (Bcl2l11). The bivalent promoter of
myeloid lineage cells. Recently, the role of lncRNAs has the BCL2L11 gene undergoes regulation through histone
been reported in regulating immune cell growth and marks, with Histone K27 methylation (H3K27me3)
functions, including their formation, differentiation, serving to repress its expression, a process counteracted
25
activation, and polarization. Table 1 below summarizes by Histone K4 methylation (H3K4me3). LncMorrbid
the role of lncRNAs in the development, polarization, and orchestrates this regulatory mechanism by recruiting the
activation of both myeloid and lymphoid cells within the polycomb repressive complex 2 (PRC2), which deposits
immune response. H3K27me3 histone marks at the BCL2L11 locus. This
concerted action prevents the expression of the BCL2L11
2.1. Role of lncRNAs in the development and gene, thereby exerting influence over the lifespan and fate
polarization of macrophage of myeloid cells. 8,25,26,37
Macrophages, expansive phagocytic myeloid cells found in The non-coding transcript in T cells (NTT), a 17-kb
various tissues, hold a crucial position in innate immunity unspliced polyadenylated lncRNA located on chromosome
and actively participate in a range of biological processes. 6q23 – q24, was initially identified in human CD4+ T cells
These include the engulfment of dying cells, processing and peripheral blood mononuclear cells. Interestingly, it is

Table 1. LncRNAs in myeloid cell development and functions
LncRNA Cell type Type Function References
MORRBID (Gm14005) Myeloid cells Intergenic It regulates the survival of short-lived myeloid cells by cis-regulating the 26
(granulocyte) expression of Bcl2l11.
NTT Monocytes Intergenic It complexes with hnRNP-U, binding to the PBOV1 gene promoter and 27
inducing cell cycle arrest. This event initiates differentiation into M0-M2,
elevates IL‑10 and CXCL10 mRNA levels, and upregulates costimulatory
molecules.
PACER (COX2‑lncRNA) Monocytes Antisense It displaces the NF-κB1 homodimer from the COX2 promoter, facilitating 28
the binding of the activating RELA/NF-κB1 heterodimer for transcription
initiation.
Lnc‑MC Monocytes Intergenic It enhances monocyte differentiation by amplifying the effects of PU.1, 29
sequestering miR-199a-5p, and upregulating ACVR1B expression.
TCONS_00019715 Monocytes Intergenic It promotes macrophage polarization towards the pro-inflammatory (M1) 30
phenotype.
HOTAIR Monocytes Antisense Facilitates the breakdown of IkBα, leading to an increase in 31
pro-inflammatory NF-κB signaling.
Lnc‑DC DCs Intergenic Enhances STAT3 signaling by binding to the STAT3 C-terminus, 32
inhibiting SHP1-mediated dephosphorylation of STAT3 at Y705.
HOTAIRM1 DCs Intergenic Promotes monocyte/DC differentiation by competitively binding to 33
endogenous miR-3960.
NEAT DCs Antisense It promotes a tolerogenic phenotype in DCs by targeting miR-3076-3p. 34,35
MALAT1 (NEAT2) DCs Intergenic Serving as a miR-155 sponge and boosting PU.1 expression, it induces a 36
tolerogenic phenotype in DCs, fostering the polarization of regulatory T
cells (Treg) through increased PU.1 expression.
Abbreviations: LncRNAs: Long non-coding RNAs; DC: Dendritic cells; IL-10: Interleukin-10.

Volume 3 Issue 2 (2024) 4 doi: 10.36922/gpd.2791