Winston Chang

CXCR6-dependent ILC3 migration to the intestinal stem cell compartment promotes epithelial regeneration after conditioning-related intestinal injury

Ya–Yuan Fu, Winston Chang, Anastasiya Ergorova, Alan M. Hanash

Abstract Interleukin-22 (IL-22) has been shown to promote epithelial regeneration, protect the intestinal stem cell (ISC) compartment from damage after allogeneic bone marrow transplantation, and reduce the severity of gastrointestinal graft vs. host disease (GI GVHD). The endogenous tissue-protective IL-22 response is …

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Post-transplant cyclophosphamide facilitates preservation of intestinal innate lymphoid cells and intestinal stem cells.

Guillermo Ortí, Rachel Lorenc, Anastasiya Ergorova, Marco Calafiore et autres

Abstract Background Type 3 innate lymphoid cells (ILC3s) produce Interleukin-22 (IL-22) and contribute to epithelial maintenance and regeneration in the intestines. However, graft vs. host disease (GVHD) leads to ILC3 loss, impairing IL-22-driven intestinal regeneration. Post-transplant cyclophosphamide (PT-Cy) is administered to prevent …

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Paneth Cells Provide a Unique Source of EGF for Intestinal Epithelium in Radiation Injury That Is Dispensable in Gvhd.

Winston Chang, Viktor Arnhold, Ya–Yuan Fu, Marco Calafiore et autres

Paneth cells (PCs) are a secretory epithelial population located in small intestine (SI) crypts. PCs produce growth factors within the intestinal stem cell (ISC) niche, including WNT3 , DLL1 and EGF, that maintain the intestinal epithelium . In murine models of acute …

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STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration

Shuichiro Takashima, Roshan Sharma, Winston Chang, Marco Calafiore et autres

The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal …

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Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage

Viktor Arnhold, Winston Chang, Suze A. Jansen, Govindarajan Thangavelu et autres

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 …

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IL-33 Induces Paneth Cell Production of EGF and Soluble ST2, Regulating Epithelial Regeneration after Intestinal Injury

Marco Calafiore, Ya–Yuan Fu, Paola Vinci, Viktor Arnhold et autres

Crypt base intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but their frequencies are reduced in experimental models of graft vs. host disease (GVHD). Paneth cells provide an epithelial contribution to the stem cell niche, but their frequencies are …

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Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis

Rui Miao, Cong Jiang, Winston Chang, Haiwei Zhang et autres

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

Marco Calafiore, Ya–Yuan Fu, Paola Vinci, Viktor Arnhold et autres

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored …

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Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia

Claire T. Deakin, Bianca Lucia De Stavola, Geoffrey Owen Littlejohn, Hedley Griffiths et autres

Importance: There is a need for observational studies to supplement evidence from clinical trials, and the target trial emulation (TTE) framework can help avoid biases that can be introduced when treatments are compared crudely using observational data by applying design principles for …

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Donor-Derived Amphiregulin Drives CD4+ T Cell Expansion and Promotes Tissue Pathology after Experimental Allogeneic BMT

Takahiro Ito, Shuichiro Takashima, Marco Calafiore, Ya–Yuan Fu et autres

Amphiregulin (Areg), a ligand for the epidermal growth factor receptor (EGFR), contributes to cell proliferation and survival. Work in recent years has demonstrated that immune cells such as Tregs and ILC2s can produce Areg, leading to tissue repair after injury. In the …

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Corticosteroid Treatment Impairs Epithelial Regeneration, Limiting Intestinal Recovery in Experimental Graft Vs Host Disease

Viktor Arnhold, Suze A. Jansen, Winston Chang, Govindarajan Thangavelu et autres

Abstract Corticosteroids (CS) represent first-line treatment for gastrointestinal graft vs host disease (GI GVHD), and CS failure is associated with severe morbidity and mortality. While the immune system is the intended target of CS treatment, the glucocorticoid receptor (GR) is widely expressed, …

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Immune-Mediated Reprogramming of Intestinal Stem Cells Drives STAT1-Dependent Myc Expression and Epithelial Regeneration in GI-Gvhd

Shuichiro Takashima, Roshan Sharma, Anastasiya Egorova, Jason Kuttiyara et autres

Abstract Crypt apoptosis and regeneration are characteristic findings in GI-GVHD. Intestinal stem cells (ISCs) are critical for maintaining the intestinal epithelium, but their frequencies are reduced in experimental GVHD, and the mechanisms driving crypt regeneration in this context are poorly understood. To …

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