Abstract
CD31, a trans-homophilic inhibitory receptor expressed on both T- and B-lymphocytes, drives the mutual detachment of interacting leukocytes. Intriguingly, T cell CD31 molecules relocate to the immunological synapse (IS), where the T and B cells establish a stable interaction.Here, we show that intact CD31 molecules, which are able to drive an inhibitory signal, are concentrated at the periphery of the IS but are excluded from the center of the IS. At this site, were the cells establish the closest contact, the CD31 molecules are cleaved, and most of the extracellular portion of the protein, including the trans-homophilic binding sites, is shed from the cell surface.T cells lacking CD31 trans-homophilic binding sites easily establish stable interactions with B cells; at the opposite, CD31 signaling agonists inhibit T/B IS formation as well as the ensuing helper T cell activation and function. Confocal microscopy and flow cytometry analysis of experimental T/B IS shows that the T cell inhibitory effects of CD31 agonists depend on SHP-2 signaling, which reduces the phosphorylation of ZAP70.The analysis of synovial tissue biopsies from patients affected by rheumatoid arthritis showed that T cell CD31 molecules are excluded from the center of the T/B cell synapses invivo. Interestingly, the administration of CD31 agonists invivo significantly attenuated the development of the clinical signs of collagen-induced arthritis in DBA1/J mice.Altogether, our data indicate that the T cell co-inhibitory receptor CD31 prevents the formation of functional T/B immunological synapses and that therapeutic strategies aimed at sustaining CD31 signaling will attenuate the development of autoimmune responses invivo.
| Original language | English |
|---|---|
| Pages (from-to) | 23-33 |
| Number of pages | 11 |
| Journal | Journal of Autoimmunity |
| Volume | 56 |
| DOIs | |
| Publication status | Published - Jan 1 2015 |
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Keywords
- Autoimmune arthritis
- CD31
- Immunological synapse
- Inhibitory receptors
- ITIM
- T lymphocytes
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
Upholding the T cell immune-regulatory function of CD31 inhibits the formation of T/B immunological synapses invitro and attenuates the development of experimental autoimmune arthritis in vivo. / Clement, Marc; Fornasa, Giulia; Loyau, Stéphane; Morvan, Marion; Andreata, Francesco; Guedj, Kevin; Khallou-Laschet, Jamila; Larghi, Paola; Le Roux, Delphine; Bismuth, Georges; Chiocchia, Gilles; Hivroz, Claire; Newman, Debra K.; Nicoletti, Antonino; Caligiuri, Giuseppina.
In: Journal of Autoimmunity, Vol. 56, 01.01.2015, p. 23-33.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Upholding the T cell immune-regulatory function of CD31 inhibits the formation of T/B immunological synapses invitro and attenuates the development of experimental autoimmune arthritis in vivo
AU - Clement, Marc
AU - Fornasa, Giulia
AU - Loyau, Stéphane
AU - Morvan, Marion
AU - Andreata, Francesco
AU - Guedj, Kevin
AU - Khallou-Laschet, Jamila
AU - Larghi, Paola
AU - Le Roux, Delphine
AU - Bismuth, Georges
AU - Chiocchia, Gilles
AU - Hivroz, Claire
AU - Newman, Debra K.
AU - Nicoletti, Antonino
AU - Caligiuri, Giuseppina
PY - 2015/1/1
Y1 - 2015/1/1
N2 - CD31, a trans-homophilic inhibitory receptor expressed on both T- and B-lymphocytes, drives the mutual detachment of interacting leukocytes. Intriguingly, T cell CD31 molecules relocate to the immunological synapse (IS), where the T and B cells establish a stable interaction.Here, we show that intact CD31 molecules, which are able to drive an inhibitory signal, are concentrated at the periphery of the IS but are excluded from the center of the IS. At this site, were the cells establish the closest contact, the CD31 molecules are cleaved, and most of the extracellular portion of the protein, including the trans-homophilic binding sites, is shed from the cell surface.T cells lacking CD31 trans-homophilic binding sites easily establish stable interactions with B cells; at the opposite, CD31 signaling agonists inhibit T/B IS formation as well as the ensuing helper T cell activation and function. Confocal microscopy and flow cytometry analysis of experimental T/B IS shows that the T cell inhibitory effects of CD31 agonists depend on SHP-2 signaling, which reduces the phosphorylation of ZAP70.The analysis of synovial tissue biopsies from patients affected by rheumatoid arthritis showed that T cell CD31 molecules are excluded from the center of the T/B cell synapses invivo. Interestingly, the administration of CD31 agonists invivo significantly attenuated the development of the clinical signs of collagen-induced arthritis in DBA1/J mice.Altogether, our data indicate that the T cell co-inhibitory receptor CD31 prevents the formation of functional T/B immunological synapses and that therapeutic strategies aimed at sustaining CD31 signaling will attenuate the development of autoimmune responses invivo.
AB - CD31, a trans-homophilic inhibitory receptor expressed on both T- and B-lymphocytes, drives the mutual detachment of interacting leukocytes. Intriguingly, T cell CD31 molecules relocate to the immunological synapse (IS), where the T and B cells establish a stable interaction.Here, we show that intact CD31 molecules, which are able to drive an inhibitory signal, are concentrated at the periphery of the IS but are excluded from the center of the IS. At this site, were the cells establish the closest contact, the CD31 molecules are cleaved, and most of the extracellular portion of the protein, including the trans-homophilic binding sites, is shed from the cell surface.T cells lacking CD31 trans-homophilic binding sites easily establish stable interactions with B cells; at the opposite, CD31 signaling agonists inhibit T/B IS formation as well as the ensuing helper T cell activation and function. Confocal microscopy and flow cytometry analysis of experimental T/B IS shows that the T cell inhibitory effects of CD31 agonists depend on SHP-2 signaling, which reduces the phosphorylation of ZAP70.The analysis of synovial tissue biopsies from patients affected by rheumatoid arthritis showed that T cell CD31 molecules are excluded from the center of the T/B cell synapses invivo. Interestingly, the administration of CD31 agonists invivo significantly attenuated the development of the clinical signs of collagen-induced arthritis in DBA1/J mice.Altogether, our data indicate that the T cell co-inhibitory receptor CD31 prevents the formation of functional T/B immunological synapses and that therapeutic strategies aimed at sustaining CD31 signaling will attenuate the development of autoimmune responses invivo.
KW - Autoimmune arthritis
KW - CD31
KW - Immunological synapse
KW - Inhibitory receptors
KW - ITIM
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=84920288556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920288556&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2014.09.002
DO - 10.1016/j.jaut.2014.09.002
M3 - Article
C2 - 25277651
AN - SCOPUS:84920288556
VL - 56
SP - 23
EP - 33
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -