An immunologist's guide to CD31 function in T-cells

Marelli‐Berg, Federica M.; Clément, Marc; Mauro, Claudio; Caligiuri, Giuseppina

doi:10.1242/jcs.124099

Cited by 112 publications

(93 citation statements)

References 89 publications

(116 reference statements)

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“…No expression of regulatory markers was seen in T FH from any source. CD31 is a key molecule for the regulation of T cell homeostasis, effector function, and trafficking (17)(18)(19). We found an increased expression of CD31 on the surface of circulating follicular cells, whereas the tonsil-derived counterparts did not express this marker.…”

Section: Human Circulating T Fr Comprise a Phenotypically Distinct Pomentioning

confidence: 64%

“…We showed that although the expression of Foxp3 and Helios was the same in T FR , blood-derived follicular cells are CD31 + whereas the tonsil-derived follicular cells are negative. It has been reported that CD31 expression regulates T cell activation and can thus prevent hyperactivation (17,19). In addition, recent evidence showed that the loss of CD31 after activation leads to a stable interaction of T cells with B cells (18).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis

Dhaeze

Peelen

Hombrouck

et al. 2015

The Journal of Immunology

103

134

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Follicular regulatory T cells (TFR) have been extensively characterized in mice and participate in germinal center responses by regulating the maturation of B cells and production of (auto)antibodies. We report that circulating TFR are phenotypically distinct from tonsil-derived TFR in humans. They have a lower expression of follicular markers, and display a memory phenotype and lack of high expression of B cell lymphoma 6 and ICOS. However, the suppressive function, expression of regulatory markers, and FOXP3 methylation status of blood TFR is comparable with tonsil-derived TFR. Moreover, we show that circulating TFR frequencies increase after influenza vaccination and correlate with anti-flu Ab responses, indicating a fully functional population. Multiple sclerosis (MS) was used as a model for autoimmune disease to investigate alterations in circulating TFR. MS patients had a significantly lower frequency of circulating TFR compared with healthy control subjects. Furthermore, the circulating TFR compartment of MS patients displayed an increased proportion of Th17-like TFR. Finally, TFR of MS patients had a strongly reduced suppressive function compared with healthy control subjects. We conclude that circulating TFR are a circulating memory population derived from lymphoid resident TFR, making them a valid alternative to investigate alterations in germinal center responses in the context of autoimmune diseases, and TFR impairment is prominent in MS.

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Section: Human Circulating T Fr Comprise a Phenotypically Distinct Pomentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis

Dhaeze

Peelen

Hombrouck

et al. 2015

The Journal of Immunology

103

134

View full text Add to dashboard Cite

show abstract

“…14 While the role of CD31-expressing lymphocytes are best defined in T cells, it is postulated that activated NK cells use homotypic CD31 interactions to lyse CD4 1 T cells, B cells and dendritic cells. 44 The Ly49 receptor family is not the only receptor pathway involved in uNK cell activation. Two other receptors activated by non-MHC ligands, aryl hydrocarbon receptor and natural cytotoxicity triggering receptor 1 (the human NKp46 homologue), independently activate uNK cells.…”

Section: Discussionmentioning

confidence: 99%

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Lima

Rahim

et al. 2014

Cell Mol Immunol

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In humans, specific patterns of killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer (uNK) cells are linked through HLA-C with pregnancy complications (infertility, recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia). To identify mechanisms underpinning the associations between NK cell activation and pregnancy success, pregnancies were studied in mice with genetic knockdown (KD) of the MHC-activated Ly49 receptor gene family. B6.Ly49 KD pregnancies were compared to normal control B6.Ly49 129 and C57BL/6 (B6) pregnancies. At mid-pregnancy (gestation day (gd9.5)), overall uNK cell (TCRb 2 CD122 1 DBA 1 DX5 2 (DBA 1 DX5 2 )) and TCRb 2 CD122 1 DBA 2 DX5 1 (DBA 2 DX5 1 )) frequencies in pregnant uterus were similar between genotypes. Ly49 KD lowered the normal frequencies of Ly49 1 uNK cells from 90.3% to 47.8% in DBA 2 DX5 1 and 78.8% to 6.3% in DBA 1 DX5 2 uNK cell subtypes. B6.Ly49 KD matings frequently resulted in expanded blastocysts that did not implant (subfertility). B6.Ly49 KD mice that established pregnancy had gestational lengths and litter sizes similar to controls. B6.Ly49 KD neonates, however, were heavier than controls. B6.Ly49 KD implantation sites lagged in early (gd6.5) decidual angiogenesis and were deficient in mid-pregnancy (gd10.5) spiral arterial remodelling. Ultrastructural analyses revealed that B6.Ly49 KD uNK cells had impaired granulogenesis, while immunocytochemistry revealed deficient vascular endothelial cell growth factor (VEGFA) production. Perforin and IFNG expression were normal in B6.Ly49 KD uNK cells. Thus, in normal mouse pregnancies, Ly49 receptor signaling must promote implantation, early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances in these functions may underlie the reported genetic associations between human pregnancy complications and the inability of specific conceptus MHCs to engage activating KIR on uNK cells.

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“…As expected, only exogenous BMDCs were able to elicit the production of effector cytokines in functional tests, provided that they had not been conditioned with CD31. Discussion CD31 is an important, yet neglected, immune inhibitory receptor (8,9,29). Because of its extracellular Ig-like domains and localization in the lateral junctions between endothelial cells in the vasculature (30), CD31 was initially viewed as a putative celladhesion molecule, and the ability of CD31-targeting antibodies or recombinant proteins (31, 32) to inhibit leukocyte transmigration has long supported this perception.…”

Section: Ifn-mentioning

confidence: 99%

CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells

Clément

Fornasa

Guedj

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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CD31 is a transhomophilic tyrosine-based inhibitory motif receptor and is expressed by both dendritic cells (DCs) and T lymphocytes. Previous studies have established that the engagement of CD31 drives immune-inhibitory signaling in T lymphocytes, but the effect exerted by CD31 signaling in DCs remains elusive. Here, we show that CD31 is a key coinhibitory receptor on stimulated DCs, favoring the development of tolerogenic functions and finally resulting in T-cell tolerance. The disruption of CD31 signaling favored the immunogenic maturation and migration of resident DCs to the draining lymph nodes. In contrast, sustaining the CD31/SHP-1 signaling during DC maturation resulted in reduced NF-κB nuclear translocation, expression of costimulatory molecules, and production of immunogenic cytokines (e.g., IL-12, IL-6), whereas the expression of TGF-β and IL-10 were increased. More importantly, CD31-conditioned DCs purified from the draining lymph nodes of ovalbuminimmunized mice favored the generation of antigen-specific regulatory T cells (CD25 + forkhead box P3 + ) at the expense of effector (IFN-γ + ) cells upon coculture with naive ovalbumin-specific CD4 + T lymphocytes ex vivo. Finally, the adoptive transfer of CD31-conditioned myelin oligodendrocyte glycoprotein-loaded DCs carried immune tolerance against the subsequent development of MOG-induced experimental autoimmune encephalomyelitis in vivo. The key coinhibitory role exerted by CD31 on DCs highlighted by the present study may have important implications both in settings where the immunogenic function of DCs is desirable, such as infection and cancer, and in settings where tolerance-driving DCs are preferred, such as autoimmune diseases and transplantation.CD31 tolerance | NFkB | Treg | EAE

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An immunologist's guide to CD31 function in T-cells

Cited by 112 publications

References 89 publications

Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis

Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

CD31 is a key coinhibitory receptor in the development of immunogenic dendritic cells

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