Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression
(2009) In Journal of Immunology 182(10). p.6508-6516- Abstract
- An important regulatory suppressive function in autoimmune and other inflammatory processes has been ascribed to CD4(+) Foxp3(+) regulatory T cells (Tregs), which requires direct cell-cell communication between Tregs, effector T cells, and APCs. However, the molecular basis for these interactions has not yet been clarified. We show here that sialoadhesin (Sn), the prototype of the siglec family of sialic acid-binding transmembrane proteins, expressed by resident and activated tissue-infiltrating macrophages, directly binds to Tregs, negatively regulating their expansion in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In this model, macrophages infiltrate the CNS exhibiting tissue-destructing... (More)
- An important regulatory suppressive function in autoimmune and other inflammatory processes has been ascribed to CD4(+) Foxp3(+) regulatory T cells (Tregs), which requires direct cell-cell communication between Tregs, effector T cells, and APCs. However, the molecular basis for these interactions has not yet been clarified. We show here that sialoadhesin (Sn), the prototype of the siglec family of sialic acid-binding transmembrane proteins, expressed by resident and activated tissue-infiltrating macrophages, directly binds to Tregs, negatively regulating their expansion in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In this model, macrophages infiltrate the CNS exhibiting tissue-destructing and demyelinating activity, leading to MS-like symptoms. We show here that severity of EAE symptoms is reduced in Sn knockout (KO) mice compared with wild-type littermates due to an up-regulation of CD4(+)Foxp3(+) Treg lymphocytes. Through the use of a Sn fusion protein, Tregs were shown to express substantial amounts of Sri ligand on their cell surface, and direct interaction of Sn+ macrophages with Tregs specifically inhibited Treg but not effector T lymphocyte proliferation. Conversely, blocking of Sn on macrophages by Sn-specific Abs resulted in elevated proliferation of Tregs. Data indicate that Sn+ macrophages regulate Treg homeostasis which subsequently influences EAE progression. We propose a new direct cell-cell interaction-based mechanism regulating the expansion of the Tregs during the immune response, representing a "dialogue" between Sn+ macrophages and Sn-accessible sialic acid residues on Treg lymphocytes. The Journal of Immunology, 2009, 182: 6508-6516. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1425948
- author
- Wu, Chuan ; Rauch, Uwe LU ; Korpos, Eva ; Song, Jian ; Loser, Karin ; Crocker, Paul R. and Sorokin, Lydia M.
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 182
- issue
- 10
- pages
- 6508 - 6516
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000265899800070
- scopus:77349113383
- pmid:19414805
- ISSN
- 1550-6606
- DOI
- 10.4049/jimmunol.0804247
- language
- English
- LU publication?
- yes
- id
- 988e8639-ec48-4357-b116-cec98626d3aa (old id 1425948)
- date added to LUP
- 2016-04-01 14:29:10
- date last changed
- 2022-03-14 06:04:33
@article{988e8639-ec48-4357-b116-cec98626d3aa,
abstract = {{An important regulatory suppressive function in autoimmune and other inflammatory processes has been ascribed to CD4(+) Foxp3(+) regulatory T cells (Tregs), which requires direct cell-cell communication between Tregs, effector T cells, and APCs. However, the molecular basis for these interactions has not yet been clarified. We show here that sialoadhesin (Sn), the prototype of the siglec family of sialic acid-binding transmembrane proteins, expressed by resident and activated tissue-infiltrating macrophages, directly binds to Tregs, negatively regulating their expansion in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In this model, macrophages infiltrate the CNS exhibiting tissue-destructing and demyelinating activity, leading to MS-like symptoms. We show here that severity of EAE symptoms is reduced in Sn knockout (KO) mice compared with wild-type littermates due to an up-regulation of CD4(+)Foxp3(+) Treg lymphocytes. Through the use of a Sn fusion protein, Tregs were shown to express substantial amounts of Sri ligand on their cell surface, and direct interaction of Sn+ macrophages with Tregs specifically inhibited Treg but not effector T lymphocyte proliferation. Conversely, blocking of Sn on macrophages by Sn-specific Abs resulted in elevated proliferation of Tregs. Data indicate that Sn+ macrophages regulate Treg homeostasis which subsequently influences EAE progression. We propose a new direct cell-cell interaction-based mechanism regulating the expansion of the Tregs during the immune response, representing a "dialogue" between Sn+ macrophages and Sn-accessible sialic acid residues on Treg lymphocytes. The Journal of Immunology, 2009, 182: 6508-6516.}},
author = {{Wu, Chuan and Rauch, Uwe and Korpos, Eva and Song, Jian and Loser, Karin and Crocker, Paul R. and Sorokin, Lydia M.}},
issn = {{1550-6606}},
language = {{eng}},
number = {{10}},
pages = {{6508--6516}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression}},
url = {{http://dx.doi.org/10.4049/jimmunol.0804247}},
doi = {{10.4049/jimmunol.0804247}},
volume = {{182}},
year = {{2009}},
}