Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018133 (
graft-versus-host disease
)
18,032
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In an ex vivo mouse model, regulatory transplantation tolerance is not only linked to Foxp3, but also to release of leukaemia inhibitory factor (LIF) and to expression of
axotrophin
(also known as MARCH-7), a putative ubiquitin E3 ligase associated with feedback control of T cell activation and of T cell-derived LIF. Given this coordinate correlation with tolerance, we now ask if Foxp3 expression is influenced by LIF or by
axotrophin
. In spleen cells from allo-rejected mice we found that exogenous LIF reduced interferon gamma release in response to donor antigen by 50%, but LIF had no direct effect on levels of Foxp3 protein in allo-primed cells that were either tolerant, or aggressive, for donor antigen. However, we did find an effect of
axotrophin
on Foxp3: in the
axotrophin
null mouse, thymic Foxp3 transcripts were reduced compared to
axotrophin
wildtype littermates. To test whether these findings in the mouse were of potential significance in man we measured transcript levels of
axotrophin
and LIF in peripheral blood cell samples collected for a recently published clinical study concerning haematopoietic stem cell recipients. In controls, human peripheral blood CD4+CD25+cells contained significantly more FOXP3 and
axotrophin
than CD4+CD25-cells. In bone marrow autograft recipients, where peripheral blood cell samples directly represent both the grafted tissue and the immune response, both FOXP3 and
axotrophin
negatively correlated with
graft versus host disease
(
GVHD
). These data suggest that (i) thymic Foxp3+T cell development is influenced by
axotrophin
; and (ii) clinical auto-
GVHD
inversely correlates with
axotrophin
transcript expression as has been previously reported for FOXP3.
...
PMID:Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance. 1716 53
