Kalkman, HO and Feuerbach, Dominik (2017) Microglia M2A-polarization as potential link between food allergy and autism spectrum disorders. Pharmaceuticals, 10 (95). ISSN 1424-8247

Abstract

Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD). Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4, IL5 and IL13), which stimulate microglia and macrophages to adopt a phenotype referred to as ‘alternative activation’ or ‘M2A’. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mTOR, and thereby to the inhibition of autophagy. Notably, activation of mTOR is an effect that is common to several of the syndromic forms of autism. Inhibition of autophagy results in diminished removal of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases would represent a risk factor for autism spectrum disorders.

Item Type:	Article
Date Deposited:	23 Dec 2017 00:45
Last Modified:	23 Dec 2017 00:45
URI:	https://oak.novartis.com/id/eprint/32559