Adoptively transferred in vitro-generated myeloid-derived suppressor cells improve T-cell function and antigen-specific immunity after traumatic lung injury

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JIN525088.pdf (1.04 MB)

Date

2022-06-10

Authors

Kustermann, Monika
Dasari, Prasad
Knape, Ingrid
Keltsch, Emma
Liu, Jianing
Pflüger, Silvia
Osen, Wolfram
Holzmann, Karlheinz
Huber-Lang, Markus
Debatin, Klaus-Michael

Journal Title

Journal ISSN

Volume Title

Publication Type

Wissenschaftlicher Artikel

DOI

https://doi.org/10.18725/OPARU-54856

Published in

Journal of Innate Immunity, 2022

Abstract

Abstract Immune reactions after trauma are characterized by immediate activation of innate immunity and simultaneously downregulation of adaptive immunity leading to a misbalanced immunohomeostasis and immunosuppression of the injured host. Therefore, the susceptibility to secondary infections is strongly increased after trauma. Immune responses are regulated by a network of immune cells influencing each other and at the same time modifying their functions dependent on the inflammatory environment. Although myeloid-derived suppressor cells (MDSCs) are initially described as T-cell suppressors, their immunomodulatory capacity after trauma is mostly undefined. Therefore, in vitro-generated MDSCs were adoptively transferred into mice after blunt chest trauma (TxT). A single MDSC treatment-induced splenic T-cell expansion decreased apoptosis sensitivity and improved proliferation in the absence of T-cell exhaustion until 2 weeks after trauma. MDSC treatment had a long-lasting effect on the genomic landscape of CD4 + T cells by upregulating primarily Th2-associated genes. Remarkably, immune-activating functions of MDSCs supported the ability of TxT mice to respond to post-traumatic secondary antigen challenge. Secondary insults were mimicked by immunizing MDSC-treated TxT mice with ovalbumin (OVA), followed by OVA restimulation in vitro. MDSC treatment significantly increased the frequency of OVA-specific T cells, enhanced their Th1/Th2 cytokine expression, and induced upregulation of cytolytic molecules finally improving OVA-specific cytotoxicity. Overall, we could show that therapeutic MDSC treatment after TxT improves post-traumatic T-cell functions, which might enable the traumatic host to counterbalance trauma-induced immunoparalysis. © In Copyright http://rightsstatements.org/vocab/InC/1.0/

Description

Faculties

Medizinische Fakultät

Institutions

UKU. Klinik für Kinder- und Jugendmedizin
UKU. Klinik für Innere Medizin III
UKU. Institut für Klinische und Experimentelle Trauma-Immunologie

Citation

DFG Project uulm

SFB 1149 Teilprojekt A01 / Späte Schrankenstörung nach experimentellem und klinischem Polytrauma / DFG / 251293561

EU Project THU

Other projects THU

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CC BY-NC International

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Part of

DOI external

DOI external

10.1159/000525088

Institutions

Periodical

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DFG Project THU

item.page.thu.projectEU

item.page.thu.projectOther

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Keywords

Immunotherapy, Myeloid-derived suppressor cells, Trauma, Cellular immunity, Post-traumatic immunosuppression, Secondary infection, DDC 610 / Medicine & health