A20 deletion in T cells modulates acute graft-versus-host disease in mice

Fischer JC, Otten V, Steiger K, Schmickl M, Slotta-Huspenina J, Beyaert R, Van Loo G, Peschel C, Poeck H, Haas T, Spoerl S (2017)

Publication Type: Journal article

Publication year: 2017

Journal

European Journal of Immunology Wiley-VCH Verlag

Book Volume: 47

Pages Range: 1982-1988

Journal Issue: 11

DOI: 10.1002/eji.201646911

Abstract

The NF-κB 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-γ and systemic inflammation was 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.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Universiteit Gent (UGent) / Ghent University BE Belgium (BE)

How to cite

APA:

Fischer, J.C., Otten, V., Steiger, K., Schmickl, M., Slotta-Huspenina, J., Beyaert, R.,... Spoerl, S. (2017). A20 deletion in T cells modulates acute graft-versus-host disease in mice. European Journal of Immunology, 47(11), 1982-1988. https://dx.doi.org/10.1002/eji.201646911

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.

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