Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis

Scherlinger, Marc; Guillotin, Vivien; Douchet, Isabelle; Vacher, Pierre; Boizard-Moracchini, Andréa; Guégan, Jean-Philippe; Garreau, Anne; Merillon, Nathalie; Vermorel, Agathe; Ribeiro, E.; Machelart, Irène; Lazaro, Estibaliz; Couzi, Lionel; Duffau, Pierre; Barnetche, Thomas; Pellegrin, Jean‐Luc; Viallard, Jean‐François; Saleh, Maya; Schaeverbeke, Thierry; Legembre, Patrick; Truchetet, Marie-Élise; Dumortier, Hélène; Contin‐Bordes, Cécile; Sisirak, Vanja; Richez, Christophe; Blanco, Patrick

doi:10.1126/scitranslmed.abi4994

Cited by 22 publications

(22 citation statements)

References 55 publications

(79 reference statements)

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“…A recent study has identified that P‐selectin glycoprotein ligand‐1 (PSGL‐1), an adhesion molecule that can be expressed by T cells, 248 , 249 is highly expressed on Tfrs (Figure 3 ) in patients with SLE. 250 PSGL‐1 interaction with selectin impaired the suppression function of Tfrs and contributed to the pathogenesis of SLE via inhibition of the TGF‐β pathway and reduced expression of FOXP3. Moreover, the circulating P‐selectin derived from platelets was activated and correlated with disease severity in the patients with SLE.…”

Section: Treg Subsets In Autoimmune Diseasementioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

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CD4 + CD25 + regulatory T cells (Tregs), a subpopulation of naturally CD4 + T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. The functions and mechanisms of different phenotypes of Tregs in different disease settings, such as tumor microenvironment, autoimmune diseases, and transplantation, have gradually become hot spots of immunology research that arouse extensive attention. Among the complex functions, CD4 + CD25 + FOXP3 + Tregs possess a potent immunosuppressive capacity and can produce various cytokines, such as IL‐2, IL‐10, and TGF‐β, to regulate immune homeostasis. They can alleviate the progression of diseases by resisting inflammatory immune responses, whereas promoting the poor prognosis of diseases by helping cells evade immune surveillance or suppressing effector T cells activity. Therefore, methods for targeting Tregs to regulate their functions in the immune microenvironment, such as depleting them to strengthen tumor immunity or expanding them to treat immunological diseases, need to be developed. Here, we discuss that different subpopulations of Tregs are essential for the development of immunotherapeutic strategies involving Tregs in human diseases.

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Section: Treg Subsets In Autoimmune Diseasementioning

confidence: 99%

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Jiang

Zhu

Wang

et al. 2022

MedComm

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“…This leads to inhibition of the regulatory and suppressive properties of T reg cells and particularly follicular T reg cells. As a result, P-selectin engagement on T reg cells limits immunosuppressive and regulatory responses of T reg cells [ 25 ].…”

Section: Cellular Adhesion Moleculesmentioning

confidence: 99%

Adhesion molecules: a way to understand lupus

Nowak¹,

Gumkowska-Sroka²,

Kotyla³

2022

Reumatologia

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Systemic lupus erythematosus is a connective disease in which all vitally important organs may be affected. The etiology of the disease is largely unknown and almost all immunological mechanisms have been proposed as the pathophysiological background of the disease. Among them, endothelial damage and dysfunction seem to play a pivotal role. Endothelial damage can be accurately measured using adhesion molecules such asintercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), platelet endothelial cell adhesion molecule (PECAM) and selectins. In this review we discuss the role of well-known cellular adhesion molecules as pathogenic factors in disease development as well as disease activity biomarkers.

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“…In addition to their role in hemostasis and thrombosis, they are active immune cells and may also be involved in processes leading to chronic inflammation and autoimmunity 1 . This view of platelets as cells participating in inflammation and immunity is based on observations, showing for example that platelets interact directly with classical immune cells and that mediators contained in platelet granules as well as de novo produced platelet derived cytokines can modulate both innate and adaptive immunity 2,3 . The role of these mediators and interactions in SLE, including interactions with immune complex, complement and shedding of CD40 ligand (CD40L), are being investigated 1 .…”

Section: Introductionmentioning

confidence: 99%

“…We and others have observed that platelet size determined by flow cytometry forward scatter (FSC) and mean platelet volume (MPV) are decreased in patients with SLE [8][9][10] , but there are no clear consensus regarding the role of platelet size in SLE 11,12 . Platelets from SLE patients also show signs of being degranulated, depleted in serotonin and are a major source of 3…”

Section: Introductionmentioning

confidence: 99%

“… 1 This view of platelets as cells participating in inflammation and immunity is based on observations, showing for example that platelets interact directly with classical immune cells and that mediators contained in platelet granules as well as de novo produced platelet derived cytokines can modulate both innate and adaptive immunity. 2 3 The role of these mediators and interactions in systemic lupus erythematosus (SLE), including interactions with immune complex (IC), complement, and shedding of CD40 ligand (CD40L), are being investigated. 1 Platelets are known to express several complement proteins and receptors and they promote and actively initiate complement activation on the platelet surface.…”

Section: Introductionmentioning

confidence: 99%

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Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus

et al. 2022

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Background SLE is a complex disease characterized by autoimmunity towards apoptotic cells, excessive amounts of circulating immune complexes and complement activation. Decreased platelet size has been observed in SLE and their non-hemostatic functions may play an active role in the disease. Our main objective in this study was to find clues that could explain their decreased size and functional role, analyzing the entire platelet proteome. Methods and patients Platelets were isolated from 23 patients with SLE. The five individuals with highest and lowest average platelet forward scatter were selected for further analysis. Platelet protein content was analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) and compared to platelets from five healthy controls (HC) Data are available via ProteomeXchange with identifier PXD031202. Results Out of 2572 proteins identified, 396 had significantly different levels (ANOVA q-value ≤ 0.01). Forty proteins, including immunoglobulin-, complement- and phosphatidylserine binding proteins had higher abundance in platelets from SLE patients, largely independent of size (fold difference of ≥ 1.5 and a t-test p-value of ≤ 0.05 as cut off). Functional characterization revealed increased degranulation and skewed hemostatic balance in platelets from SLE patients. In the SLE proteome, immunoglobulin proteins were negatively correlated to serum complement C3 and C4 and the highest relative levels was detected in platelets of normal size. Conclusion Platelets from SLE patients shared a specific protein profile, including immunoglobulins, complement proteins and autoantigens, largely independent of platelet size and in agreement with an integrated role for platelets in SLE.

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Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis

Cited by 22 publications

References 55 publications

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity

Adhesion molecules: a way to understand lupus

Enrichment of Complement, Immunoglobulins, and Autoantibody Targets in the Proteome of Platelets from Patients with Systemic Lupus Erythematosus

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