Suppressor T helper type 17 cell responses in intestinal transplant recipients with allograft rejection
Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Intestinal transplant (ITx) rejection is associated with memory T helper type 17 cell (Th17) infiltration of grafted tissues. Modulation of Th17 effector cell response is facilitated by T regulatory (Treg) cells, but a phenotypic characterization of this process is lacking in the context of allograft rejection.
METHODS: Flow cytometry was performed to examine the expression of surface receptors, cytokines, and transcription factors in Th17 and Treg cells in ITx control (n = 34) and rejection patients (n = 23). To elucidate key pathways guiding the rejection biology, we utilized RNA sequencing (RNAseq) and assessed epigenetic stability through pyrosequencing of the Treg-specific demethylated region (TSDR).
RESULTS: We found that intestinal allograft rejection is characterized by Treg cellular infiltrates, which are polarized toward Th17-type chemokine receptor, ROR-γt transcription factor expression, and cytokine production. These Treg cell subsets have maintained epigenetic stability, as defined by FoxP3-TSDR methylation status, but displayed upregulation of functional Treg and purinergic signaling genes by RNAseq analysis such as CD39, in keeping with suppressor Th17 properties.
CONCLUSION: We show that ITx rejection is associated with increased polarized cells that express a Th17-like phenotype concurrent with regulatory purinergic markers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Human immunology - (2024) vom: 16. März, Seite 110773 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Belyayev, Leonid [VerfasserIn] |
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Date Revised 17.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.humimm.2024.110773 |
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| PPN (Katalog-ID): |
NLM369840755 |
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| 520 | |a Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Intestinal transplant (ITx) rejection is associated with memory T helper type 17 cell (Th17) infiltration of grafted tissues. Modulation of Th17 effector cell response is facilitated by T regulatory (Treg) cells, but a phenotypic characterization of this process is lacking in the context of allograft rejection | ||
| 520 | |a METHODS: Flow cytometry was performed to examine the expression of surface receptors, cytokines, and transcription factors in Th17 and Treg cells in ITx control (n = 34) and rejection patients (n = 23). To elucidate key pathways guiding the rejection biology, we utilized RNA sequencing (RNAseq) and assessed epigenetic stability through pyrosequencing of the Treg-specific demethylated region (TSDR) | ||
| 520 | |a RESULTS: We found that intestinal allograft rejection is characterized by Treg cellular infiltrates, which are polarized toward Th17-type chemokine receptor, ROR-γt transcription factor expression, and cytokine production. These Treg cell subsets have maintained epigenetic stability, as defined by FoxP3-TSDR methylation status, but displayed upregulation of functional Treg and purinergic signaling genes by RNAseq analysis such as CD39, in keeping with suppressor Th17 properties | ||
| 520 | |a CONCLUSION: We show that ITx rejection is associated with increased polarized cells that express a Th17-like phenotype concurrent with regulatory purinergic markers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a FoxP3 | |
| 650 | 4 | |a Intestinal transplantation | |
| 650 | 4 | |a Th17 | |
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| 700 | 1 | |a Kang, Jiman |e verfasserin |4 aut | |
| 700 | 1 | |a Sadat, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Loh, Katrina |e verfasserin |4 aut | |
| 700 | 1 | |a Patil, Digvijay |e verfasserin |4 aut | |
| 700 | 1 | |a Muralidaran, Vinona |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Khalid |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufman, Stuart |e verfasserin |4 aut | |
| 700 | 1 | |a Subramanian, Sukanya |e verfasserin |4 aut | |
| 700 | 1 | |a Gusev, Yuriy |e verfasserin |4 aut | |
| 700 | 1 | |a Bhuvaneshwar, Krithika |e verfasserin |4 aut | |
| 700 | 1 | |a Ressom, Habtom |e verfasserin |4 aut | |
| 700 | 1 | |a Varghese, Rency |e verfasserin |4 aut | |
| 700 | 1 | |a Ekong, Udeme |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumoto, Cal S |e verfasserin |4 aut | |
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| 700 | 1 | |a Fishbein, Thomas M |e verfasserin |4 aut | |
| 700 | 1 | |a Kroemer, Alexander |e verfasserin |4 aut | |
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