Sunday, September 25, 2011

blind love: neuro-immune chemistry

Immune and nervous systems share two unique characteristics: (a) both systems undergo adaptive “education” to discriminate between self and nonself signals and (b) both systems have “memory” to it.

So far few research papers had been published that addressed the question how these two complex systems interact with each other. For example, one paper claimed that T cells can promote neuronal re-generation and hence contribute to the learning process (1). These study was based on evidence that T cell transfer into immunodeficient mice improved neuronal generation. In my opinion, this interpretation fails to take into account the fact that T cell transfer into immunodeficient mice affect not just brain function but for instance, gut permeability too. Why is it important? It is well known that endotoxin (LPS) level in the blood affects brain function. LPS level in the blood, in turn, is influenced by gut permeability, that in turn, is influenced by immune system status. T cell transfer into immunodeficient mice would allow differentiation of gut-homing T cells that may have reduced gut permeability thus indirectly affecting brain function.

If you are interested in neuro-immune research, then I will recommend to read the following two papers recently published in Science (2, 3).

1st paper from Kevin Tracey's Lab provided the direct evidence that the presence of specialized, acetylcholine-secreting memory T cells were necessary and sufficient to relay signals from nervous system to the immune (2).

2nd paper from Paul Kubes Lab showed that CD1d-deficient mice (that lack all NKT cells) were more susceptible to stroke-associated immunosuppression compared to wild-type mice (3). This immunosuppression could be prevented by stimulating NKT cells or blocking noradrenalin signaling in these cells because this protective effect of noradrenalin blockade was abolished in CD1d-deficient mice. It is of note that both NKT presence and simultaneous blockade of noradrenalin signaling in these cells was necessary for full protection. This is a kind of paradox. However, because there are two types of NKT cells in mice, there may be a simple explanation. So it will be interesting to compare CD1d-deficient mice to Jalpha18-deficient mice that lack only one type of NKT cells. In my opinion, NKT cells transfer into CD1d-deficient mice would have provided more direct evidence of protective role of this innate NKT cells.

David Usharauli

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