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2. Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage

Author

Arnhold, Viktor, Chang, Winston Y., Jansen, Suze A., Thangavelu, Govindarajan, Calafiore, Marco, Vinci, Paola, Fu, Ya-Yuan, Ito, Takahiro, Takashima, Shuichiro, Egorova, Anastasiya, Kuttiyara, Jason, Perlstein, Adam, van Hoesel, Marliek, Liu, Chen, Blazar, Bruce R., Lindemans, Caroline A., and Hanash, Alan M.

Subjects
Thermo Fisher Scientific Inc., Scientific equipment and supplies industry -- Analysis, Gene expression -- Analysis, T cells -- Analysis, Corticosteroids -- Analysis, Genes -- Analysis, Intestines -- Analysis, Stem cells -- Analysis, Immunotherapy -- Analysis, Disease susceptibility -- Analysis, Health care industry, The Jackson Laboratory, Memorial Sloan-Kettering Cancer Center
Abstract

Corticosteroid treatment (CST) failure is associated with poor outcomes for patients with gastrointestinal (GI) graft-versus-host disease (GVHD). CST is intended to target the immune system, but the glucocorticoid receptor (GR) is widely expressed, including within the intestines, where its effects are poorly understood. Here, we report that corticosteroids (CS) directly targeted intestinal epithelium, potentially worsening immune-mediated GI damage. CS administered to mice in vivo and intestinal organoid cultures ex vivo reduced epithelial proliferation. Following irradiation, immediate CST mitigated GI damage but delayed treatment attenuated regeneration and exacerbated damage. In a murine steroid-refractory (SR) GVHD model, CST impaired epithelial regeneration, worsened crypt loss, and reduced intestinal stem cell (ISC) frequencies. CST also exacerbated immune-mediated damage in organoid cultures with SR, GR-deficient T cells or IFN-[gamma]. These findings correlated with CS-dependent changes in apoptosis-related gene expression and STAT3-related epithelial proliferation. Conversely, IL-22 administration enhanced STAT3 activity and overcame CS-mediated attenuation of regeneration, reducing crypt loss and promoting ISC expansion in steroid-treated mice with GVHD. Therefore, CST has the potential to exacerbate GI damage if it fails to control the damage-inducing immune response, but this risk may be countered by strategies augmenting epithelial regeneration, thus providing a rationale for clinical approaches combining such tissue- targeted therapies with immunosuppression., Introduction The epithelial lining of the gastrointestinal (GI) tract undergoes turnover every 5-7 days (1). This renewal is maintained by the cycling of leucine-rich, repeat-containing GPCR 5-positive ([Lgr5.sup.+]) intestinal stem [...]

Published
2024
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3. Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses

Author

Krasemann, Susanne, Dittmayer, Carsten, von Stillfried, Saskia, Meinhardt, Jenny, Heinrich, Fabian, Hartmann, Kristin, Pfefferle, Susanne, Thies, Edda, von Manitius, Regina, Aschman, Tom Alex David, Radke, Josefine, Osterloh, Anja, Schmid, Simone, Buhl, Eva Miriam, Ihlow, Jana, Dubois, Frank, Arnhold, Viktor, Elezkurtaj, Sefer, Horst, David, Hocke, Andreas, Timm, Sara, Bachmann, Sebastian, Corman, Victor, Goebel, Hans-Hilmar, Matschke, Jakob, Stanelle-Bertram, Stephanie, Gabriel, Gülsah, Seilhean, Danielle, Adle-Biassette, Homa, Ondruschka, Benjamin, Ochs, Matthias, Stenzel, Werner, Heppner, Frank L., Boor, Peter, Radbruch, Helena, Laue, Michael, and Glatzel, Markus

Published
2022
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4. Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage

Author

MS Algemene Pediatrie Onderzoek 2, Cluster B, SCT patientenzorg, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Arnhold, Viktor, Chang, Winston Y., Jansen, Suze A., Thangavelu, Govindarajan, Calafiore, Marco, Vinci, Paola, Fu, Ya Yuan, Ito, Takahiro, Takashima, Shuichiro, Egorova, Anastasiya, Kuttiyara, Jason, Perlstein, Adam, van Hoesel, Marliek, Liu, Chen, Blazar, Bruce R., Lindemans, Caroline A., Hanash, Alan M., MS Algemene Pediatrie Onderzoek 2, Cluster B, SCT patientenzorg, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Arnhold, Viktor, Chang, Winston Y., Jansen, Suze A., Thangavelu, Govindarajan, Calafiore, Marco, Vinci, Paola, Fu, Ya Yuan, Ito, Takahiro, Takashima, Shuichiro, Egorova, Anastasiya, Kuttiyara, Jason, Perlstein, Adam, van Hoesel, Marliek, Liu, Chen, Blazar, Bruce R., Lindemans, Caroline A., and Hanash, Alan M.

Published
2024

5. A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury

Author

Cluster B, CMM, Cancer, Hubrecht Institute with UMC, Infection & Immunity, Regenerative Medicine and Stem Cells, Child Health, SCT patientenzorg, Calafiore, Marco, Fu, Ya Yuan, Vinci, Paola, Arnhold, Viktor, Chang, Winston Y., Jansen, Suze A., Egorova, Anastasiya, Takashima, Shuichiro, Kuttiyara, Jason, Ito, Takahiro, Serody, Jonathan, Nakae, Susumu, Turnquist, Heth, van Es, Johan, Clevers, Hans, Lindemans, Caroline A., Blazar, Bruce R., Hanash, Alan M., Cluster B, CMM, Cancer, Hubrecht Institute with UMC, Infection & Immunity, Regenerative Medicine and Stem Cells, Child Health, SCT patientenzorg, Calafiore, Marco, Fu, Ya Yuan, Vinci, Paola, Arnhold, Viktor, Chang, Winston Y., Jansen, Suze A., Egorova, Anastasiya, Takashima, Shuichiro, Kuttiyara, Jason, Ito, Takahiro, Serody, Jonathan, Nakae, Susumu, Turnquist, Heth, van Es, Johan, Clevers, Hans, Lindemans, Caroline A., Blazar, Bruce R., and Hanash, Alan M.

Published
2023

6. Paneth Cell Niche Function Is Dispensable in Gvhd

Author

Arnhold, Viktor, primary, Chang, Winston, additional, Fu, Ya-Yuan, additional, Vinci, Paola, additional, Takashima, Shuichiro, additional, Ito, Takahiro, additional, Egorova, Anastasiya, additional, Kuttiyara, Jason, additional, Liu, Chen, additional, Calafiore, Marco, additional, and Hanash, Alan M., additional

Published
2023
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10. The Amphiregulin/EGFR Axis Regulates Donor T Cell Expansion and Contributes to Intestinal Gvhd Pathology after Allogeneic Bone Marrow Transplantation

Author

Ito, Takahiro, primary, Takashima, Shuichiro, additional, Calafiore, Marco, additional, Fu, Ya-Yuan, additional, Egorova, Anastasiya, additional, Kuttiyara, Jason, additional, Chang, Winston, additional, Vinci, Paola, additional, Arnhold, Viktor, additional, Zaiss, Dietmar, additional, and Hanash, Alan M., additional

Published
2022
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11. IL-22 Treatment Overcomes Corticosteroid-Mediated Suppression of Epithelial Regeneration and Exacerbation of Gvhd-Associated GI Damage

Author

Arnhold, Viktor, primary, Jansen, Suze A., additional, Chang, Winston, additional, Thangavelu, Govindarajan, additional, Vinci, Paola, additional, Takashima, Shuichiro, additional, Egorova, Anastasiya, additional, Kuttiyara, Jason, additional, Liu, Chen, additional, Calafiore, Marco, additional, Blazar, Bruce R., additional, Lindemans, Caroline A., additional, and Hanash, Alan M., additional

Published
2022
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12. Corticosteroid Treatment Impairs Epithelial Regeneration, Limiting Intestinal Recovery in Experimental Graft Vs Host Disease

Author

Arnhold, Viktor, primary, Jansen, Suze A, additional, Chang, Winston, additional, Thangavelu, Govindarajan, additional, Vinci, Paola, additional, Takashima, Shuichiro, additional, Egorova, Anastasiya, additional, Kuttiyara, Jason, additional, van Hoesel, Marliek, additional, Liu, Chen, additional, Calafiore, Marco, additional, Blazar, Bruce R., additional, Lindemans, Caroline, additional, and Hanash, Alan M, additional

Published
2021
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20. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

Author

Arnhold, Viktor, primary, Schmelz, Karin, additional, Proba, Jutta, additional, Winkler, Annika, additional, Wünschel, Jasmin, additional, Toedling, Joern, additional, Deubzer, Hedwig E., additional, Künkele, Annette, additional, Eggert, Angelika, additional, Schulte, Johannes H., additional, and Hundsdoerfer, Patrick, additional

Published
2017
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