Depletion of Natural Killer Cells improve cholestasis in a murine model of primary biliary cholangitis
Abstract Background and Objective: The aim of this study is to investigate the role of NK cells and their phenotypes in xenobiotic induced murine model of primary biliary cholangitis （PBC）by eliminating NK cells. Methods: C57BL/6 female mice were immunized with 2OA-BSA and poly I:C to develop the murine model of PBC. Serologic, histologic, and immunologic testing of PBC mice were analyzed by depleting NK cells with ASGM1 before (ASGM1+PBC group) or after immunization (PBC+ASGM1 group). The proportions of NK cells, CD62L+NK cells, CD4+, and CD8+T in liver were analyzed. Results: ALT, AST and ALP in PBC mice was increased. In contrast to PBC mice, AST in ASGM1+PBC group was decreased. Moreover, TBIL was decreased in PBC+ASGM1 group. Notably, ALP and titer of AMA in mice treated with ASGM1 was decreased when compared with PBC mice. Comparing with HC, ASGM1+PBC or PBC+ASGM1 group mice, the ratio of CD4+T cells in liver declined in PBC mice. In comparison to HC and ASGM1+PBC group mice, the ratio of CD4+/CD8+T cells in PBC mice was lower. The frequency of CD62L+NK cells in the liver of PBC mice increased. However, there was no significant difference in histological scores among ASGM1+PBC, PBC+ASGM1 and PBC mice. Conclusions: Eliminating NK cells could reduce the degree of cholestasis and improve the immune imbalance. NK cells were functionally involved in pathogenesis and disease progression, especially CD62L+NK cells in liver might aggravate the progression of PBC..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 08. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Bin [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.21203/rs.3.rs-2978477/v1 |
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| PPN (Katalog-ID): |
XRA039774953 |
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| 520 | |a Abstract Background and Objective: The aim of this study is to investigate the role of NK cells and their phenotypes in xenobiotic induced murine model of primary biliary cholangitis （PBC）by eliminating NK cells. Methods: C57BL/6 female mice were immunized with 2OA-BSA and poly I:C to develop the murine model of PBC. Serologic, histologic, and immunologic testing of PBC mice were analyzed by depleting NK cells with ASGM1 before (ASGM1+PBC group) or after immunization (PBC+ASGM1 group). The proportions of NK cells, CD62L+NK cells, CD4+, and CD8+T in liver were analyzed. Results: ALT, AST and ALP in PBC mice was increased. In contrast to PBC mice, AST in ASGM1+PBC group was decreased. Moreover, TBIL was decreased in PBC+ASGM1 group. Notably, ALP and titer of AMA in mice treated with ASGM1 was decreased when compared with PBC mice. Comparing with HC, ASGM1+PBC or PBC+ASGM1 group mice, the ratio of CD4+T cells in liver declined in PBC mice. In comparison to HC and ASGM1+PBC group mice, the ratio of CD4+/CD8+T cells in PBC mice was lower. The frequency of CD62L+NK cells in the liver of PBC mice increased. However, there was no significant difference in histological scores among ASGM1+PBC, PBC+ASGM1 and PBC mice. Conclusions: Eliminating NK cells could reduce the degree of cholestasis and improve the immune imbalance. NK cells were functionally involved in pathogenesis and disease progression, especially CD62L+NK cells in liver might aggravate the progression of PBC. | ||
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