Class I MHC & neuroplasticity - a novel role for a classical immune molecule

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Inflammation is the body's response to acute or chronic challenge. Infection and injury lead to activation of the innate and/or adaptive arms of the immune system. Hallmarks of inflammation (redness, heat, swelling, pain) were first described more than 2000 years ago by the Roman medical writer Cornelius Celcus (1 AD) and the added feature of loss of function was added in the 19th century. Inflammation is a common feature of disease but is also a necessary component of our body's normal homeostasis. Interestingly, immune signaling of the innate and adaptive immune system is just as important to maintaining good health as it is to disease. In the past few decades, the importance of immune-brain communication to brain health has moved to the forefront of neuroscience and psychiatry. Research efforts have established a role for immune molecules and related signaling systems in normal brain development, neuronal excitability, neurotransmission, neuroplasticity, and behaviour. Evidence shows that molecules originally thought to be unique to the immune system are present and functional in the brain. In fact, the brain and immune system share many molecules including neurotransmitters and their receptors, cytokines and chemokines and their receptors, integrins, and cell adhesion molecules to name a few. The discovery that immune molecules may have non-immune roles in the brain changes the way that we may think about the immune system and has stimulated new research directions aimed at identifying novel roles for immune molecules in normal brain function.Class I MHC is a classical immune molecule with an established role in adaptive immunity. Despite the large body of knowledge on class I MHC immune function, the exact nature and range of its functional possibilities in brain has not been extensively analyzed. Since its presence in neurons was revealed, direct evidence has been provided for its role in normal neuronal development and synaptic plasticity in adult neurons. Work by myself and others demonstrated that its expression profile is dynamic and it acts to some degree as a cellular indicator of stress specifically, its expression is increased in specific neuronal populations dictated by the nature of the stimulus. Our body of work has described changes in class I MHC mRNA expression in neurons in response to both immune and non-immune challenges. Work by others has also demonstrated the functional importance of class I MHC to plasticity in adult hippocampal neurons. Together this evidence suggests that class I MHC neuronal signalling may be important to neuronal viability and function. Importantly, through our NSERC-funded research program, we are learning more about how this immune molecule has dual roles in health and disease. Knowledge gained by this work will provide novel ideas about these roles and encourage more consideration of body-brain interactions in mental wellness and general brain health.