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\begin{document}

\title{Combination therapy of anti-TNF nanobody and PGE2 elevated therapeutic
effect in experimental colits via regulating Treg/Th17 balance}



\author[1]{Xing Liu}%
\author[1]{Mingkai Ni}%
\author[2]{Lulu Zhou}%
\author[1]{Zichun Hua}%
\affil[1]{Nanjing University}%
\affil[2]{China Pharmaceutical University}%


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  \date{May 27, 2024}


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\begin{abstract}
Abstract Backgrounds and purpose: Anti-TNF therapy have gained great
success in autoimmune disease. However, insufficient efficacy and safety
of high dosage anti-TNF agents are exposed in amounts of clinical cases.
Aiming at improving therapeutic of anti-TNF therapy, an anti-TNF
nanobody V19 and combination therapy with PGE2 was introduced.
Experimental Approach: DSS-induced colitis mice was used for evaluating
therapeutic effect of V19 and combination therapy. Variation of
Treg/Th17 balance was raised as the criterion for comparing therapeutic
with combination therapy and mono-therapy. Key Results: V19 expressed by
Escherichia. coil showed therapeutic effect on DSS-induced colitis mice
by inducing the increase of treg via up-regulating tm-TNF-\selectlanguage{greek}α \selectlanguage{english}and TNFR2 in
peripheral blood. However, cell apoptosis (treg, Dendritic Cells and CD8
T cells) was induced in peripheral blood under high dose of V19
accompanied with up-regulated tm-TNF-\selectlanguage{greek}α. \selectlanguage{english}Besides, Th17 cells in colons
from DSS-induced mice were induced by V19 accompanied with up-regulation
of IL-6. Combination therapy presented better therapeutic effect than
mono-therapy. After combination therapy, Th17 cells were significantly
decreased in colons and vitro assay demonstrated that PGE2 reduced Th17
cells by down-regulating IL-6 in colons via EP4. Although PGE2 showed no
influence on cell apoptosis and can not induce treg generation, it
enhanced the ability of V19 in inducing treg by up-regulating TNFR2 via
EP4 in peripheral blood. Conclusion: This combination therapy presents
good clinical significance that combination of PGE2 can expand drug
delivery window and enhanced therapeutic effect during the anti-TNF
clinical treatment.%
\end{abstract}%



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