Advanced

Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression

Wu, Chuan; Rauch, Uwe LU ; Korpos, Eva; Song, Jian; Loser, Karin; Crocker, Paul R. and Sorokin, Lydia M. (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:
author
organization
publishing date
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
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
2009-06-26 14:22:31
date last changed
2017-03-19 03:55:05
@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},
  volume       = {182},
  year         = {2009},
}