Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders

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 and IL13), which stimulate microglia and macrophages to adopt a phenotype...

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Main Authors: Hans O. Kalkman, Dominik Feuerbach
Format: Article
Language:English
Published: MDPI AG 2017-12-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/10/4/95
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spelling doaj-0ec20a79e3504fcc8f8dd153754e88522020-11-25T03:29:32ZengMDPI AGPharmaceuticals1424-82472017-12-011049510.3390/ph10040095ph10040095Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum DisordersHans O. Kalkman0Dominik Feuerbach1Gänsbühlgartenweg 7, CH4132 Muttenz, SwitzerlandNovartis Pharma AG, CH4002 Basel, SwitzerlandAtopic 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 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 (BDNF) 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 mammalian Target of Rapamycin (mTOR), and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.https://www.mdpi.com/1424-8247/10/4/95mast cellTh2 cellinterleukin 4insulin-like growth factorautophagysynaptic pruning
collection DOAJ
language English
format Article
sources DOAJ
author Hans O. Kalkman
Dominik Feuerbach
spellingShingle Hans O. Kalkman
Dominik Feuerbach
Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
Pharmaceuticals
mast cell
Th2 cell
interleukin 4
insulin-like growth factor
autophagy
synaptic pruning
author_facet Hans O. Kalkman
Dominik Feuerbach
author_sort Hans O. Kalkman
title Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
title_short Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
title_full Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
title_fullStr Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
title_full_unstemmed Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders
title_sort microglia m2a polarization as potential link between food allergy and autism spectrum disorders
publisher MDPI AG
series Pharmaceuticals
issn 1424-8247
publishDate 2017-12-01
description 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 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 (BDNF) 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 mammalian Target of Rapamycin (mTOR), and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.
topic mast cell
Th2 cell
interleukin 4
insulin-like growth factor
autophagy
synaptic pruning
url https://www.mdpi.com/1424-8247/10/4/95
work_keys_str_mv AT hansokalkman microgliam2apolarizationaspotentiallinkbetweenfoodallergyandautismspectrumdisorders
AT dominikfeuerbach microgliam2apolarizationaspotentiallinkbetweenfoodallergyandautismspectrumdisorders
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