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Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria
Signal regulatory protein alpha (SIRPα/CD172a) is a conserved transmembrane protein thought to play an inhibitory role in immune function by binding the ubiquitous ligand CD47. SIRPα expression has been used to identify dendritic cell subsets across species and here we examined its expression and fu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284040/ https://www.ncbi.nlm.nih.gov/pubmed/25236797 http://dx.doi.org/10.1002/eji.201444859 |
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author | Scott, Charlotte L TFP, Zangerle Murray Beckham, Katherine S H Douce, Gillian Mowat, Allan McI |
author_facet | Scott, Charlotte L TFP, Zangerle Murray Beckham, Katherine S H Douce, Gillian Mowat, Allan McI |
author_sort | Scott, Charlotte L |
collection | PubMed |
description | Signal regulatory protein alpha (SIRPα/CD172a) is a conserved transmembrane protein thought to play an inhibitory role in immune function by binding the ubiquitous ligand CD47. SIRPα expression has been used to identify dendritic cell subsets across species and here we examined its expression and function on intestinal DCs in mice. Normal mucosa contains four subsets of DCs based on their expression of CD103 and CD11b and three of these express SIRPα. However, loss of SIRPα signaling in mice leads to a selective reduction in the CD103(+)CD11b(+) subset of DCs in the small intestine, colon, and among migratory DCs in the mesenteric lymph node. In parallel, these mice have reduced numbers of T(H)17 cells in steady-state intestinal mucosa, and a defective T(H)17 response to Citrobacter infection. Identical results were obtained in CD47KO mice. DC precursors from SIRPα mutant mice had an enhanced ability to generate CD103(+)CD11b(+) DCs in vivo, but CD103(+)CD11b(+) DCs from mutant mice were more prone to die by apoptosis. These data show a previously unappreciated and crucial role for SIRPα in the homeostasis of CD103(+)CD11b(+) DCs in the intestine, as well as providing further evidence that this subset of DCs is critical for the development of mucosal T(H)17 responses. |
format | Online Article Text |
id | pubmed-4284040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42840402015-01-14 Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria Scott, Charlotte L TFP, Zangerle Murray Beckham, Katherine S H Douce, Gillian Mowat, Allan McI Eur J Immunol Immunomodulation Signal regulatory protein alpha (SIRPα/CD172a) is a conserved transmembrane protein thought to play an inhibitory role in immune function by binding the ubiquitous ligand CD47. SIRPα expression has been used to identify dendritic cell subsets across species and here we examined its expression and function on intestinal DCs in mice. Normal mucosa contains four subsets of DCs based on their expression of CD103 and CD11b and three of these express SIRPα. However, loss of SIRPα signaling in mice leads to a selective reduction in the CD103(+)CD11b(+) subset of DCs in the small intestine, colon, and among migratory DCs in the mesenteric lymph node. In parallel, these mice have reduced numbers of T(H)17 cells in steady-state intestinal mucosa, and a defective T(H)17 response to Citrobacter infection. Identical results were obtained in CD47KO mice. DC precursors from SIRPα mutant mice had an enhanced ability to generate CD103(+)CD11b(+) DCs in vivo, but CD103(+)CD11b(+) DCs from mutant mice were more prone to die by apoptosis. These data show a previously unappreciated and crucial role for SIRPα in the homeostasis of CD103(+)CD11b(+) DCs in the intestine, as well as providing further evidence that this subset of DCs is critical for the development of mucosal T(H)17 responses. BlackWell Publishing Ltd 2014-12 2014-10-27 /pmc/articles/PMC4284040/ /pubmed/25236797 http://dx.doi.org/10.1002/eji.201444859 Text en © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA Weinheim http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Immunomodulation Scott, Charlotte L TFP, Zangerle Murray Beckham, Katherine S H Douce, Gillian Mowat, Allan McI Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title | Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title_full | Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title_fullStr | Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title_full_unstemmed | Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title_short | Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103(+)CD11b(+) DCs in the intestinal lamina propria |
title_sort | signal regulatory protein alpha (sirpα) regulates the homeostasis of cd103(+)cd11b(+) dcs in the intestinal lamina propria |
topic | Immunomodulation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284040/ https://www.ncbi.nlm.nih.gov/pubmed/25236797 http://dx.doi.org/10.1002/eji.201444859 |
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