Abstract Dr. Mohan L. Sopori
Title:
Neuro Immune Modulation: Structure and function of nicotinic receptors on T
cells
Synopsis:
The
central nervous system and the immune system communicate bidirectionally and the
cholinergic system plays an important role in this neuro-immune modulation. Both
neurons and immune cells express nicotinic and muscarinic cholinergic receptors.
Chronic exposure to cigarette smoke/nicotine causes immunosuppression and
increases susceptibility to infections. Nicotine is also antiinflammatory and
several inflammatory and allergic diseases are less prevalent in smokers than in
non-smokers. Nicotine regulates the immune systems through the autonomic nervous
system and through direct interaction with T cells. T cells express α7-nicotinic
acetylcholine receptors (α7-nAChRs) that are essentially identical in sequence
to the neuronal α7-nAChR. However, while in neurons, α7-nAChRs are ligand gated
cation channels that primarily permeate Ca2+ into the cells, in T cells,
nicotine-induced rise in intracellular Ca2+ is independent of the nicotine
responsive ligand-gated Ca2+ channels. Nicotine modulates two distinct signaling
pathways in T cells: 1. Nicotine-induced rise in intracellular Ca2+ requires a
function Src-like protein tyrosine kinase, Lck and CD3/T cell receptor complex.
2. Nicotine affects NFκB activation through the ERK pathway that is independent
of the T-cell receptor and the Ca2+ response. In addition, while nicotinic
agonists inhibit the immune system, muscarinic agonists activate some of the
immune parameters. Thus, activation of muscarinic and nicotinic cholinergic
receptors may represent the yin and yang of the immune response.
Updated 09/08/2006
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