A20 deletion in T cells modulates acute graft-versus-host disease in mice
- Author
- Julius C Fischer, Vera Otten, Katja Steiger, Martina Schmickl, Julia Slotta-Huspenina, Rudi Beyaert (UGent) , Geert van Loo (UGent) , Christian Peschel, Hendrik Poeck, Tobias Haas and Silvia Spoerl
- Organization
- Abstract
- The NF-kappa B regulator A20 limits inflammation by providing negative feedback in myeloid cells and B cells. Functional lack of A20 has been linked to several inflammatory and autoimmune diseases. To define how A20 affects the functionality of T effector cells in a highly inflammatory environment, we performed conventional allogeneic hematopoietic stem cell transplantation (allo-HSCT) with A20-deficient CD4(+) and CD8(+) donor T cells in mice. Severity and mortality of graft-versus-host disease (GVHD) after allo-HSCT was drastically reduced in recipients transplanted with conventional doses of A20-deficient T cells. Consistently, we found that the A20-deficient donor T-cell compartment was strongly diminished at various timepoints after allo-HSCT. However, proportionally more A20-deficient donor T cells produced IFN-gamma and systemic inflammationwas elevated early after allo-HSCT. Consequently, increasing the dose of transplanted A20-deficient T cells reversed the original phenotype and resulted in enhanced GVHD mortality compared to recipients that received A20(+/+) T cells. Still, A20-deficient T cells, activated either through T cell receptor-dependent or -independent mechanisms, were less viable than control A20(+/+) T cells, highlighting that A20 balances both, T-cell activation and survival. Thus, our findings suggest that targeting A20 in T cells may allow to modulate T-cell-mediated inflammatory diseases like GVHD.
- Keywords
- SYSTEMIC-LUPUS-ERYTHEMATOSUS, NF-KAPPA-B, TNFAIP3, AUTOIMMUNITY, INFLAMMATION, DEFICIENCY, SURVIVAL, MODELS, A20, Allogeneic hematopoietic stem cell transplantation, Graft-versus-host disease, Inflammatory response, T cells
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8538832
- MLA
- Fischer, Julius C et al. “A20 Deletion in T Cells Modulates Acute Graft-versus-host Disease in Mice.” EUROPEAN JOURNAL OF IMMUNOLOGY 47.11 (2017): 1982–1988. Print.
- APA
- Fischer, Julius C, Otten, V., Steiger, K., Schmickl, M., Slotta-Huspenina, J., Beyaert, R., van Loo, G., et al. (2017). A20 deletion in T cells modulates acute graft-versus-host disease in mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 47(11), 1982–1988.
- Chicago author-date
- Fischer, Julius C, Vera Otten, Katja Steiger, Martina Schmickl, Julia Slotta-Huspenina, Rudi Beyaert, Geert van Loo, et al. 2017. “A20 Deletion in T Cells Modulates Acute Graft-versus-host Disease in Mice.” European Journal of Immunology 47 (11): 1982–1988.
- Chicago author-date (all authors)
- Fischer, Julius C, Vera Otten, Katja Steiger, Martina Schmickl, Julia Slotta-Huspenina, Rudi Beyaert, Geert van Loo, Christian Peschel, Hendrik Poeck, Tobias Haas, and Silvia Spoerl. 2017. “A20 Deletion in T Cells Modulates Acute Graft-versus-host Disease in Mice.” European Journal of Immunology 47 (11): 1982–1988.
- Vancouver
- 1.Fischer JC, Otten V, Steiger K, Schmickl M, Slotta-Huspenina J, Beyaert R, et al. A20 deletion in T cells modulates acute graft-versus-host disease in mice. EUROPEAN JOURNAL OF IMMUNOLOGY. 2017;47(11):1982–8.
- IEEE
- [1]J. C. Fischer et al., “A20 deletion in T cells modulates acute graft-versus-host disease in mice,” EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 47, no. 11, pp. 1982–1988, 2017.
@article{8538832,
abstract = {The NF-kappa B regulator A20 limits inflammation by providing negative feedback in myeloid cells and B cells. Functional lack of A20 has been linked to several inflammatory and autoimmune diseases. To define how A20 affects the functionality of T effector cells in a highly inflammatory environment, we performed conventional allogeneic hematopoietic stem cell transplantation (allo-HSCT) with A20-deficient CD4(+) and CD8(+) donor T cells in mice. Severity and mortality of graft-versus-host disease (GVHD) after allo-HSCT was drastically reduced in recipients transplanted with conventional doses of A20-deficient T cells. Consistently, we found that the A20-deficient donor T-cell compartment was strongly diminished at various timepoints after allo-HSCT. However, proportionally more A20-deficient donor T cells produced IFN-gamma and systemic inflammationwas elevated early after allo-HSCT. Consequently, increasing the dose of transplanted A20-deficient T cells reversed the original phenotype and resulted in enhanced GVHD mortality compared to recipients that received A20(+/+) T cells. Still, A20-deficient T cells, activated either through T cell receptor-dependent or -independent mechanisms, were less viable than control A20(+/+) T cells, highlighting that A20 balances both, T-cell activation and survival. Thus, our findings suggest that targeting A20 in T cells may allow to modulate T-cell-mediated inflammatory diseases like GVHD.},
author = {Fischer, Julius C and Otten, Vera and Steiger, Katja and Schmickl, Martina and Slotta-Huspenina, Julia and Beyaert, Rudi and van Loo, Geert and Peschel, Christian and Poeck, Hendrik and Haas, Tobias and Spoerl, Silvia},
issn = {0014-2980},
journal = {EUROPEAN JOURNAL OF IMMUNOLOGY},
keywords = {SYSTEMIC-LUPUS-ERYTHEMATOSUS,NF-KAPPA-B,TNFAIP3,AUTOIMMUNITY,INFLAMMATION,DEFICIENCY,SURVIVAL,MODELS,A20,Allogeneic hematopoietic stem cell transplantation,Graft-versus-host disease,Inflammatory response,T cells},
language = {eng},
number = {11},
pages = {1982--1988},
title = {A20 deletion in T cells modulates acute graft-versus-host disease in mice},
url = {http://dx.doi.org/10.1002/eji.201646911},
volume = {47},
year = {2017},
}
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