Sex differences in anatomic plasticity of gut neuronal–mast cell interactions

Abstract The gut wall houses mast cells that are anatomically situated near enteric neuronal fibers. Roles of specific neuropeptides in modulating function of immune components like mast cells in response to challenge with bacterial components are relatively unknown. Investigating such interactions...

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Main Authors: Luke A. Schwerdtfeger, Stuart A. Tobet
Format: Article
Language:English
Published: Wiley 2021-10-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.15066
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author Luke A. Schwerdtfeger
Stuart A. Tobet
author_facet Luke A. Schwerdtfeger
Stuart A. Tobet
author_sort Luke A. Schwerdtfeger
collection DOAJ
description Abstract The gut wall houses mast cells that are anatomically situated near enteric neuronal fibers. Roles of specific neuropeptides in modulating function of immune components like mast cells in response to challenge with bacterial components are relatively unknown. Investigating such interactions requires models that include diverse cellular elements in native anatomic arrangements. Using an organotypic slice model that maintains gut wall cellular diversity ex vivo, the present study compared responses between tissues derived from male and female mice to examine neural‐immune signaling in the gut wall after selected treatments. Ileum slices were treated with pharmacological reagents that block neuronal function (e.g., tetrodotoxin) or vasoactive intestinal peptide (VIP) receptors prior to challenge with lipopolysaccharide (LPS) to assess their influence on anatomic plasticity of VIP fibers and activation of mast cells. Sex differences were observed in the number of mucosal mast cells (c‐kit/ACK2 immunoreactive) at baseline, regardless of treatment, with female ileum tissue having 46% more ACK2‐IR mast cells than males. After challenge with LPS, male mast cell counts rose to female levels. Furthermore, sex differences were observed in the percentage of ACK2‐IR cells within 1 µm of a VIP+ neuronal fiber, and mast cell size, a metric previously tied to activation, with females having larger cells at baseline. Male mast cell sizes reached female levels after LPS challenge. This study suggests sex differences in neural‐immune plasticity and in mast cell activation both basally and in response to challenge with LPS. These sex differences could potentially impact functional neuroimmune response to pathogens.
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spelling doaj.art-bcf468fdf65c4dfa936f34b4277034412022-12-21T22:58:11ZengWileyPhysiological Reports2051-817X2021-10-01919n/an/a10.14814/phy2.15066Sex differences in anatomic plasticity of gut neuronal–mast cell interactionsLuke A. Schwerdtfeger0Stuart A. Tobet1Department of Biomedical Sciences Colorado State University Fort Collins Colorado USADepartment of Biomedical Sciences Colorado State University Fort Collins Colorado USAAbstract The gut wall houses mast cells that are anatomically situated near enteric neuronal fibers. Roles of specific neuropeptides in modulating function of immune components like mast cells in response to challenge with bacterial components are relatively unknown. Investigating such interactions requires models that include diverse cellular elements in native anatomic arrangements. Using an organotypic slice model that maintains gut wall cellular diversity ex vivo, the present study compared responses between tissues derived from male and female mice to examine neural‐immune signaling in the gut wall after selected treatments. Ileum slices were treated with pharmacological reagents that block neuronal function (e.g., tetrodotoxin) or vasoactive intestinal peptide (VIP) receptors prior to challenge with lipopolysaccharide (LPS) to assess their influence on anatomic plasticity of VIP fibers and activation of mast cells. Sex differences were observed in the number of mucosal mast cells (c‐kit/ACK2 immunoreactive) at baseline, regardless of treatment, with female ileum tissue having 46% more ACK2‐IR mast cells than males. After challenge with LPS, male mast cell counts rose to female levels. Furthermore, sex differences were observed in the percentage of ACK2‐IR cells within 1 µm of a VIP+ neuronal fiber, and mast cell size, a metric previously tied to activation, with females having larger cells at baseline. Male mast cell sizes reached female levels after LPS challenge. This study suggests sex differences in neural‐immune plasticity and in mast cell activation both basally and in response to challenge with LPS. These sex differences could potentially impact functional neuroimmune response to pathogens.https://doi.org/10.14814/phy2.15066gutintestinemast cellmucosaVIP
spellingShingle Luke A. Schwerdtfeger
Stuart A. Tobet
Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
Physiological Reports
gut
intestine
mast cell
mucosa
VIP
title Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
title_full Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
title_fullStr Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
title_full_unstemmed Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
title_short Sex differences in anatomic plasticity of gut neuronal–mast cell interactions
title_sort sex differences in anatomic plasticity of gut neuronal mast cell interactions
topic gut
intestine
mast cell
mucosa
VIP
url https://doi.org/10.14814/phy2.15066
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