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Global Translational Medicine Inflammatory and anti-inflammatory responses in HTLV1

upregulated in psoriatic skin as compared to normal skin, The previous research has shown that increased
whereas the expression of IL-22 mRNA in peripheral FOXP3 expression in patients with ATL contributes to
blood mononuclear cells of both psoriatic patients and enhanced Tregs activity, which subsequently leads to
normal controls were similar . IL-17F, which is very increased TGF-β and IL-10secretion, thus activating the
[36]
similar to IL-17, is considered an inflammatory cytokine immunosuppression phenotype observed in HAM/TSP
[13]
since it induces many pro-inflammatory cytokines and patients . As mentioned, Th17 cells, as pro-inflammatory
chemokines . IL-17F mRNA has also been reported to be cells, express ROR-γt, as a transcription factor, and secrete
[37]
associated with activated monocytes, basophils, and mast IL-17A [48,49] . ROR-γt expression has been shown to be
cells . elevated in ATL patients’ skin and other tissues, which can
[37]
be attributed to inflammatory reactions . Since Th17 cell
[40]
IL-6 is a pro-inflammatory cytokine that is a marker of
both acute and chronic inflammation . IL-6 is involved actions are regulated by Tregs, it has been hypothesized
[38]
that Tregs impairment may contribute toTh17 cell
in immune responses, inflammation, hematopoiesis, bone overreaction, leading to uncontrolled inflammation and
metabolism, and embryonic development. IL-6 plays consequently the exacerbation of inflammation in viral
various roles in chronic inflammation (closely related to infection . However, it has been indicated that Th17 cells
[40]
chronic inflammatory diseases, autoimmune diseases, and may be important for viral transmission suppression
cancer) and even in the cytokine storm of the coronavirus in some cases. A study has shown significantly lower
disease (COVID-19) . levels of Th17 cells in HAM/TSP patients compared to
[39]
4. Role of Treg/Th17 axis in human uninfected subjects and a trend toward reduced number of
T-lymphotropic virus Type 1infection IL-17-secreting cells compared to HTLV-1 asymptomatic
carriers. Th17 cell functions vary depending on the stage
The adverse inflammatory reactions resulting in the of infection and the host immune status in viral infection,
central nervous system (CNS) inflammation and tissue similar to Tregs [4,40] . Therefore, we conclude that the role
damage followingHTLV-1 infection may be caused by the of Tregs in the pathogenesis of HTLV-1 infection varies
inappropriate function of Th17 cells . The imbalance of depending on the stage of infection and the host immune
[40]
the Treg/Th17 axis is a probable factor in the pathogenesis status [4,40,45,46] .
of HTLV-1 infection because Tregs regulate the function In the pathogenesis of HTLV-1, the immunosuppressive
of Th17 cells. IL-6 contributes toTh17 cell differentiation microenvironment mediated by Tregs may have two
by suppressing FOXP3 and TGF-βgene expressions in opposing roles. On the one hand, the regulatory function
Tregs . Through direct cell interaction and the release of Tregs in suppressing immune responses may have
[38]
of anti-inflammatory cytokines, both natural and induced enabled HTLV-1 to escape host immunity, resulting in
(i) Tregs regulate the proliferation and activities of innate viral infection progression . In this scenario, Tregs could
[50]
immune cells (dendritic cells and macrophages) and worsen the HAM/TSP pathogenic process . On the other
[51]
suppress self-reactive lymphocytes, such as Th17cells . hand, HTLV-1 functionally inhibits Tregs by increasing
[41]
MT-2 is a human HTLV-1-infected cell line obtained its proliferation, which leads to potential impairment of
from the leukemic cells of ATL patients . This cell line
[42]
can be used to determine the molecular and cellular
factors that are involved in the pathogenesis of HTLV-1
infection . The majority of MT-2 are regulatory T
[43]
cells (CD4 CD25 FOXP ), which imply that HTLV-1
+
+
+
transforms infected CD4 T cells into Tregs and causes
+
clonal proliferation . Similarly, Tregs have been suggested
[42]
to be the cells most infected with HTLV-1 in patients
with ATL and HAM/TSP . The proliferation of Tregs
[4]
increases in response to HTLV-1 infection, but these cells
have been shown to be functionally impaired in vivo and
in vitro, which might be one of the mechanisms behind
the triggering inflammatory responses [4,44] . Th17-mediated
pro-inflammatory responses can enhance viral replication.
However, the contributions of Tregs and Th17 cells in
HTLV-1-associated illnesses vary depending on the stage Figure 2. Treg/Th17 imbalance in human T-lymphotropic virus Type 1
[4]
of infection and the host’s immunological state [4,40,45-47] . infection.

Volume 2 Issue 1 (2023) 3 https://doi.org/10.36922/gtm.v2i1.67