Axotrophin and Leukaemia Inhibitory Factor (LIF) in Transplantation Tolerance

Overview

Journal Philos Trans R Soc Lond B Biol Sci

Specialty Biology

Date 2005 Sep 9

PMID 16147533

Citations 12

Authors

Su M Metcalfe

Affiliations

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Abstract

Immune self-tolerance is controlled by a subset of T lymphocytes that are regulatory (Treg) and epigenetically programmed to suppress auto-reactive immune effector cells in vivo. By extrapolation, donor-specific transplantation tolerance might be controlled by donor-specific Treg that have acquired the appropriate epigenetic program for tolerance. Although such tolerance has yet to be achieved in man, proof of concept comes from mouse models where regulatory transplantation tolerance can be induced within the complex micro-environment of the spleen or draining lymph node. By studying whole spleen cell populations in a murine model of transplantation tolerance we have incorporated a complexity of environmental factors when looking for specific features that characterize tolerance versus aggression. This approach has revealed unexpected patterns of gene activity in tolerance and most notably that a novel stem cell gene, axotrophin, regulates T lymphocyte responsiveness both in terms of proliferation and in release of leukaemia inhibitory factor (LIF). Since LIF is a regulator of stem cells in addition to being a key neuropoietic cytokine, these preliminary results linking both axotrophin and LIF to transplantation tolerance lead us to propose that regulatory pathways encoded during the epigenetic development of Treg cells are related to pathways that regulate fate determination of stem cells.

Citing Articles

Multiple Sclerosis and the LIF/IL-6 Axis: Use of Nanotechnology to Harness the Tolerogenic and Reparative Properties of LIF.

Metcalfe S, Strom T, Williams A, Fahmy T Nanobiomedicine (Rij). 2018; 2:5.

PMID: 29942371 PMC: 5997376. DOI: 10.5772/60622.

Regulation of the Mdm2-p53 pathway by the ubiquitin E3 ligase MARCH7.

Zhao K, Yang Y, Zhang G, Wang C, Wang D, Wu M EMBO Rep. 2018; 19(2):305-319.

PMID: 29295817 PMC: 5797962. DOI: 10.15252/embr.201744465.

Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding.

Flach K, Ramminger E, Hilbrich I, Arsalan-Werner A, Albrecht F, Herrmann L Biochim Biophys Acta. 2014; 1842(9):1527-38.

PMID: 24905733 PMC: 4311138. DOI: 10.1016/j.bbadis.2014.05.029.

LIF-dependent signaling: new pieces in the Lego.

Mathieu M, Saucourt C, Mournetas V, Gauthereau X, Theze N, Praloran V Stem Cell Rev Rep. 2011; 8(1):1-15.

PMID: 21537995 PMC: 3285761. DOI: 10.1007/s12015-011-9261-7.

A LIF/Nanog axis is revealed in T lymphocytes that lack MARCH-7, a RINGv E3 ligase that regulates the LIF-receptor.

Thompson L, Whiston R, Rakhimov Y, Taccioli C, Liu C, Croce C Cell Cycle. 2010; 9(20):4213-21.

PMID: 20962578 PMC: 3055204. DOI: 10.4161/cc.9.20.13543.

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