Nuclear factor-kappa B inducing kinase is required for graft-versus-host disease

作者：Sanchez Valdepenas Carmen; Casanova Lucia; Colmenero Isabel; Arriero Mar; Gonzalez Africa; Lozano Nieves; Gonzalez Vicent Marta; Diaz Miguel A; Madero Luis; Fresno Manuel; Ramirez Manuel^*

来源：Haematologica-The Hematology Journal, 2010, 95(12): 2111-2118.

DOI：10.3324/haematol.2010.028829

• NF-kappa B
• NF-kappa B inducing kinase
• NIK
• graft-versus-host disease

Background
Donor T lymphocytes are directly responsible for graft-versus-host disease. Molecules important in T-cell function may, therefore, be appropriate targets for graft-versus-host disease therapy and/or prophylaxis. Here we analyzed whether nuclear factor-kappa B inducing kinase might have a role in graft-versus-host disease.
Design and Methods
We studied the expression of nuclear factor-kappa B inducing kinase in human samples from patients with graft-versus-host disease. We also explored the effect of nuclear factor-kappa B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-kappa B inducing kinase) and C57BL/6 mice (control).
Results
We detected expression of nuclear factor-kappa B inducing kinase in T-lymphocytes in the pathological lesions of patients with acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells died of a lethal form of the disease. Deficiency of nuclear factor-kappa B inducing kinase did not affect the engrafting ability of donor T cells, but severely impaired their expansion capacity early after transplantation, and aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells. Effector T lymphocytes were the T-cell subset most affected by nuclear factor-kappa B inducing kinase deficiency. We also detected lower amounts of inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the serum of mice receiving C57BL/6 T cells.
Conclusions
Our results show that nuclear factor-kappa B inducing kinase has a role in graft-versus-host disease by maintaining the viability of activated alloreactive T lymphocytes.

• 出版日期2010-12