Expression and function of CD31 in immune cells.

Expression pattern of CD31 in different immune cell populations

CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a transmembrane glycoprotein that is expressed on various cell types, including endothelial cells, platelets, and immune cells. In the context of immune cell populations, CD31 expression is dynamic and varies depending on the cell type and activation state.ref.76.5 ref.44.1 ref.44.1 ref.76.5 ref.44.1

In naive CD4+ T cells, CD31 is coexpressed with TCR excision circles (TRECs), indicating its presence in cells that have recently undergone thymic selection. However, upon activation of naive CD4+ T cells, CD31 becomes down-regulated and is subsequently lost when these cells differentiate into memory cells. This loss of CD31 expression is irreversible and serves as a phenotypic marker for memory T cells.ref.25.18 ref.25.18 ref.82.5 ref.25.19 ref.82.5

CD31 is expressed sporadically and at low levels on blood CD8+ T cells in the resting state. However, upon repeated activation, CD8+ T cells gain high levels of CD31 expression. This upregulation of CD31 on CD8+ T cells after repeated activation suggests a role for CD31 in the activation and function of CD8+ T cells.ref.25.18 ref.25.19 ref.25.18 ref.25.15 ref.71.16

Interestingly, CD31 expression is also observed on CD28nullCD8+ T cells in patients with juvenile idiopathic arthritis (JIA). This expression of CD31 on CD8+ T cells in JIA may be attributed to a post-thymic activation event. Notably, the prevalence of CD31+CD28nullCD8+ T cells is higher in patients with oligoarticular JIA compared to those with polyarticular JIA, suggesting a potential role for CD31 in the pathogenesis of JIA.ref.25.13 ref.25.20 ref.25.19 ref.25.19 ref.25.23

CD31 expression on CD4+ T cells has been shown to correlate with increased size of atherosclerotic aortic aneurysm. The loss of CD31 expression by CD4+ T cells is associated with increased severity of graft-versus-host disease after hematopoietic stem cell transplantation and atherosclerosis. These findings suggest that CD31 expression on CD4+ T cells may play a role in the development and progression of atherosclerosis.ref.44.2 ref.44.1 ref.24.27 ref.71.16 ref.71.4

Functional consequences of CD31 engagement on immune cell behavior

CD31 engagement has been shown to have functional consequences on immune cell behavior, particularly in T cells. The engagement of CD31 on T cells can modulate T cell chemokinesis and regulate T cell responses to chemokines.ref.44.9 ref.44.13 ref.44.0 ref.44.3 ref.44.2

CD31 signals have been shown to attenuate T cell chemokinesis, particularly in activated/memory T lymphocytes. This attenuation of chemokinesis is achieved by interfering with the chemokine-induced PI3K/Akt signaling pathway. As a result, the response of activated/memory T lymphocytes to chemokines is dampened. This modulation of memory T cell chemokinesis by CD31 is a key mechanism by which this molecule contributes to the homeostatic regulation of effector T cell immunity.ref.44.0 ref.44.9 ref.44.3 ref.44.6 ref.44.0

In addition to modulating T cell chemokinesis, CD31 also plays a role in the regulation of T cell activation, survival, and expansion. The engagement of CD31 on T cells can influence the strength and duration of T cell receptor (TCR) signaling, thereby impacting T cell activation. CD31 signals have been shown to promote T cell survival by activating the PI3K/Akt signaling pathway, which is important for cell survival. Furthermore, CD31 engagement on T cells can promote T cell expansion by enhancing TCR signaling and promoting cell cycle progression.ref.44.3 ref.44.0 ref.44.2 ref.44.13 ref.44.9

CD31 has also been implicated in the regulation of T cell extravasation to non-lymphoid target tissues. The expression of CD31 on endothelial cells facilitates the interaction between T cells and endothelial cells, promoting T cell transmigration across endothelial barriers. This process is important for T cell trafficking to sites of inflammation and immune responses in peripheral tissues.ref.24.26 ref.44.2 ref.94.30 ref.44.2 ref.71.16

Implications of CD31-mediated regulation of T cell function

The CD31-mediated regulation of T cell function has important implications for various inflammatory conditions, including autoimmunity and allograft rejection.ref.44.2 ref.44.0 ref.24.3 ref.24.26 ref.44.0

Loss of CD31 expression by CD4+ T cells has been associated with increased severity of atherosclerosis, suggesting that CD31 may play a protective role in the development of this inflammatory disease. Additionally, certain CD31 polymorphisms have been found to be associated with increased severity of graft-versus-host disease and atherosclerosis, further supporting the role of CD31 in these inflammatory conditions.ref.44.2 ref.24.27 ref.44.1 ref.71.16 ref.71.4

Given the role of CD31 in T cell-mediated inflammation, the therapeutic manipulation of CD31 may hold potential for controlling immune responses in various inflammatory conditions. Targeting CD31 signaling pathways could potentially modulate T cell chemokinesis, activation, survival, and extravasation, leading to the attenuation of T cell-mediated inflammation.ref.44.13 ref.44.2 ref.44.0 ref.44.2 ref.24.26

In conclusion, CD31 exhibits a dynamic expression pattern in different immune cell populations, with its expression being modulated by cell activation and differentiation. CD31 engagement on immune cells, particularly T cells, has functional consequences, including the modulation of T cell chemokinesis and regulation of T cell responses to chemokines. The CD31-mediated regulation of T cell function has implications for various inflammatory conditions, including atherosclerosis and allograft rejection. The therapeutic manipulation of CD31 may hold promise for controlling T cell-mediated inflammation and could be explored as a potential therapeutic strategy in the future.ref.44.13 ref.44.11 ref.44.0 ref.44.2 ref.44.3

Involvement of CD31 in immune cell trafficking and migration.

Introduction

CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is an immunoglobulin-like molecule expressed by leukocytes and endothelial cells. It plays a crucial role in immune cell trafficking and migration. CD31 has been shown to modulate chemokinesis in activated T lymphocytes, but not in naive T lymphocytes.ref.76.5 ref.45.20 ref.44.1 ref.94.30 ref.45.20

The signaling pathways activated downstream of CD31 engagement during immune cell migration include the PI3K/Akt signaling pathway and the ADPR/ADO production pathway. CD31 signaling is mediated mainly by two immunoreceptor tyrosine inhibitory motifs (ITIMs) in its cytoplasmic tail, which are phosphorylated upon CD31 engagement and serve as docking sites for protein-tyrosine phosphatases, including SHP-2. In this essay, we will explore the role of CD31 in immune cell trafficking and migration, its involvement in disease conditions, and the molecular mechanisms underlying its functions.ref.94.30 ref.94.30 ref.45.20 ref.44.1 ref.45.20

CD31 in Immune Cell Trafficking and Migration

A. Modulation of Chemokinesis CD31 has been shown to modulate chemokinesis, the movement of T cells in response to chemokines, in activated/memory T lymphocytes. It attenuates chemokinesis in these cells by interfering with the PI3K/Akt signaling pathway. CD31 engagement on memory T cells leads to interference with the PI3K/Akt signaling pathway, resulting in modulation of chemokinesis. CD31-mediated modulation of memory T cell chemokinesis is proposed to be a key mechanism by which CD31 contributes to the homeostatic regulation of effector T cell immunity. However, the molecular mechanisms underlying CD31-mediated regulation of T cell responses are still being investigated.ref.44.3 ref.44.0 ref.44.10 ref.44.5 ref.44.0

Loss of CD31 expression in CD4+ T cells has been associated with increased size of atherosclerotic aortic aneurysm, suggesting that CD31 is involved in immune cell homing to inflamed tissues. CD31 deficiency leads to enhanced T cell extravasation to non-lymphoid target tissues, indicating its role in inflammation. However, the molecular mechanisms underlying the involvement of CD31 in immune cell homing to lymphoid organs or inflamed tissues are not fully understood. Further research is needed to elucidate these mechanisms.ref.44.2 ref.44.1 ref.44.2 ref.44.1 ref.44.2

CD31 in Disease Conditions

A. Atherosclerosis CD31 has been implicated in the development of atherosclerosis and its clinical complications. Loss of CD31 expression by CD4+ T cells has been associated with increased size of atherosclerotic aortic aneurysm, a condition where T cell immunity plays a pathogenic role. Additionally, single nucleotide polymorphisms of CD31 have been linked to increased severity of atherosclerosis. The exact mechanisms by which CD31 contributes to the development and progression of atherosclerosis are not fully understood and require further investigation.ref.44.2 ref.44.1 ref.24.27 ref.71.16 ref.4.3

Single nucleotide polymorphisms of CD31 have also been linked to increased severity of graft-versus-host disease. Graft-versus-host disease is a complication that can occur after allogeneic hematopoietic stem cell transplantation, where immune cells from the donor attack the recipient's tissues. CD31 may play a role in regulating immune cell trafficking and migration in this context, contributing to the severity of the disease. However, the specific mechanisms by which CD31 influences graft-versus-host disease need to be explored in more detail.ref.24.27 ref.44.2 ref.24.16 ref.98.1 ref.94.30

CD31 in Leukocyte-Endothelial Interactions

CD31 is involved in leukocyte extravasation and migration by mediating interactions between leukocytes and endothelial cells. During extravasation, leukocytes undergo multiple attachments to and detachments from the vessel-lining endothelial cells before transmigrating through the endothelial cell layer and establishing residency at the tissue site. CD31 is important for the initial tethering and rolling of leukocytes on the vessel wall through interactions with selectins.ref.45.20 ref.94.30 ref.76.2 ref.40.19 ref.39.2

Subsequent firm adhesion is established through interactions with integrins. CD31 also induces the production of matrix metalloproteinases (MMPs) on leukocytes, which facilitate leukocyte invasion of tissues. These interactions and processes mediated by CD31 contribute to leukocyte-endothelial interactions during extravasation.ref.40.19 ref.76.0 ref.39.2 ref.76.2 ref.94.30

Molecular Mechanisms of CD31-Mediated Regulation

CD31 signaling is mediated mainly by two immunoreceptor tyrosine inhibitory motifs (ITIMs) in its cytoplasmic tail. Upon CD31 engagement, these ITIMs are phosphorylated and serve as docking sites for protein-tyrosine phosphatases, including SHP-2. The PI3K/Akt signaling pathway is one of the signaling pathways activated downstream of CD31 engagement during immune cell migration.ref.24.3 ref.94.32 ref.44.10 ref.44.10 ref.24.6

CD31 engagement on memory T cells leads to interference with the PI3K/Akt signaling pathway, resulting in modulation of chemokinesis. CD31-mediated immunosuppression via the ADPR/ADO production pathway has also been suggested as a mechanism of acquired resistance to PD1/PD-L1 blockade. However, the exact mechanisms by which CD31 signaling interferes with the PI3K/Akt signaling pathway and regulates T cell responses are still under investigation.ref.44.10 ref.94.30 ref.44.0 ref.44.5 ref.44.0

Conclusion

CD31 plays a crucial role in immune cell trafficking and migration. It modulates chemokinesis in activated/memory T lymphocytes by interfering with the PI3K/Akt signaling pathway. Loss of CD31 expression in CD4+ T cells has been associated with increased size of atherosclerotic aortic aneurysm, suggesting its involvement in immune cell homing to inflamed tissues.ref.44.2 ref.71.16 ref.44.1 ref.94.30 ref.44.2

CD31 deficiency leads to enhanced T cell extravasation to non-lymphoid target tissues, indicating its role in inflammation. CD31 is also involved in leukocyte-endothelial interactions during extravasation and has been implicated in the development of atherosclerosis and its clinical complications. The molecular mechanisms underlying the functions of CD31 are still being investigated, including its signaling pathways and interactions with other molecules. Further research is needed to fully understand the role of CD31 in immune cell trafficking and migration, as well as its implications in disease conditions.ref.44.1 ref.44.2 ref.24.26 ref.94.30 ref.44.2

Role of CD31 in immune cell signaling and modulation.

Introduction

CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is an immunoglobulin-like molecule that plays a crucial role in immune cell signaling and modulation. It is expressed on various cell types, including immune cells and vascular endothelial cells. CD31 signaling is mediated by the phosphorylation of immunoreceptor tyrosine inhibitory motifs (ITIMs) in its cytoplasmic tail, which serve as docking sites for protein-tyrosine phosphatases.ref.76.5 ref.44.1 ref.45.20 ref.45.20 ref.45.20

This essay will explore the intracellular signaling pathways triggered by CD31 engagement, its role in immune cell activation and proliferation, its influence on T cell responses to chemokines, and its protective effects on the vascular endothelium.ref.45.20 ref.44.1 ref.76.5 ref.45.20 ref.44.1

CD31 Signaling and Immune Cell Modulation

CD31 engagement leads to the phosphorylation of ITIMs in its cytoplasmic tail, which in turn recruit protein-tyrosine phosphatases such as SHP-2. This signaling cascade has been shown to attenuate T cell chemokinesis, particularly in activated/memory T lymphocytes, by interfering with the chemokine-induced PI3K/Akt signaling pathway. The modulation of T cell chemokinesis by CD31 signaling is specific to activated T lymphocytes and does not affect naive T lymphocytes. This suggests that CD31 plays a crucial role in fine-tuning the migration of activated T cells during immune responses.ref.24.3 ref.44.3 ref.44.0 ref.44.10 ref.44.10

Additionally, CD31 signaling confers immune privilege to the vascular endothelium and protects endothelial cells from cell-extrinsic, proapoptotic stimuli. CD31 interactions are required for endothelial cell protection from TNF-α- and CTL-induced cell death. Furthermore, CD31-mediated signals have been shown to play a protective role under conditions of immunological stress, such as T-cell-mediated inflammation and endotoxemia.ref.24.4 ref.24.3 ref.24.26 ref.24.5 ref.24.14

Loss of CD31 expression correlates with increased severity of graft-versus-host disease and atherosclerosis, highlighting the importance of CD31 signaling in regulating immune cell responses and maintaining vascular integrity.ref.44.2 ref.24.3 ref.24.14 ref.24.26 ref.24.26

CD31 and T Cell Activation and Proliferation

CD31 expression by the endothelium regulates T-cell activation and proliferation. CD31-deficient mice exhibit exaggerated disease severity in experimental models of T-cell-mediated inflammation, such as experimental autoimmune encephalomyelitis, collagen-induced arthritis, and atherosclerosis. Similarly, in humans, loss of CD31 expression by CD4+ T cells is associated with increased severity of graft-versus-host disease and atherosclerosis. These findings suggest that dysregulated CD31 signaling contributes to immunopathology in these disease conditions.ref.44.1 ref.44.2 ref.24.26 ref.71.16 ref.44.2

The molecular mechanisms underlying CD31-mediated regulation of immune cell signaling and its contribution to immunopathology are still not fully understood. Further research is needed to elucidate the specific downstream signaling events and effector molecules involved in CD31-mediated modulation of T cell activation and proliferation.ref.44.0 ref.44.2 ref.44.13 ref.44.11 ref.24.3

CD31 and T Cell Responses to Chemokines

CD31 signaling has also been implicated in the regulation of T cell responses to chemokines. CD31 engagement interferes with the chemokine-induced PI3K/Akt signaling pathway, leading to the attenuation of T cell chemokinesis. This modulation of chemokinesis is particularly evident in activated/memory T lymphocytes. By regulating T cell migration, CD31 plays a role in fine-tuning the immune response and ensuring efficient immune cell trafficking to sites of inflammation.ref.44.3 ref.44.0 ref.44.9 ref.44.10 ref.44.0

CD31 and Protection of the Vascular Endothelium

One of the critical functions of CD31 is to protect the vascular endothelium from immune-mediated damage. CD31 signaling protects endothelial cells from the intrinsic pathway of apoptosis induced by inflammatory stimuli. This protective effect is crucial for maintaining vascular integrity and preventing excessive endothelial cell death in conditions of immunological stress.ref.24.3 ref.24.4 ref.24.26 ref.24.14 ref.24.26

Furthermore, CD31 gene transfer has been shown to confer immune resistance to allogeneic targets in pancreatic β-cell transplantation. This highlights the potential therapeutic applications of CD31 in protecting transplanted tissues from immune-mediated rejection.ref.24.26 ref.24.28 ref.24.20 ref.24.16 ref.24.20

Conclusion

In conclusion, CD31 is an immunoglobulin-like molecule that plays a crucial role in immune cell signaling and modulation. CD31 signaling attenuates T cell chemokinesis, confers immune privilege to the vascular endothelium, and protects endothelial cells from immune-mediated damage. CD31 also regulates T cell activation and proliferation and modulates T cell responses to chemokines.ref.44.0 ref.44.0 ref.24.3 ref.44.2 ref.24.26

Dysregulated CD31 signaling has been implicated in immunopathology in conditions such as T-cell-mediated inflammation and atherosclerosis. Further research is needed to fully understand the molecular mechanisms underlying CD31-mediated immune cell regulation and to explore its potential therapeutic applications in immune-related diseases.ref.44.2 ref.71.16 ref.24.3 ref.44.0 ref.44.2

Works Cited