Quantitative and Functional Analysis of PD-1+ NK Cells in Patients With Autoimmune Thyroid Disease

Ortega-Rodríguez, Alma Cesleste; Martínez-Hernández, Rebeca; Monsiváis‐Urenda, Adriana; Serrano-Somavilla, Ana; Sánchez-Gutiérrez, Raquel; González‐Amaro, Roberto; Marazuela, Mónica

doi:10.1210/clinem/dgaa569

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…The coexpression of CD11c (green) and CD19 (red) appeared in yellow ( Figure 5B ). Those CD11c-expressing cells that did not colocalize with CD19 may include dendritic cells, monocytes, macrophages, granulocytes, and natural killer cells ( 43 , 44 ), which may play a complex role as antigen presenting cells and immune effector cells ( 45 – 47 ). Furthermore, we evaluated FNA samples by flow cytometry to further analyze the phenotype of CD11c + B cells in the thyroid.…”

Section: Resultsmentioning

confidence: 99%

CD11c+ B Cells Participate in the Pathogenesis of Graves’ Disease by Secreting Thyroid Autoantibodies and Cytokines

et al. 2022

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Graves’ disease (GD) is a common autoimmune disorder with an elevation in pathogenic autoantibodies, specifically anti-thyrotropin receptor antibodies (TRAbs), which are secreted by autoreactive B cells. To date, there has been little research on self-reactive B cells in GD. In the current study, we reported that a unique B-cell subset, CD11c+ B cells, was expanded in the peripheral blood (PB) of GD patients, as detected by flow cytometry. The frequency of CD11c+ B cells was positively correlated with serum TRAb levels. The flow cytometry data showed that CD11c expression was higher in a variety of B-cell subsets and that CD11c+ B cells presented a distinct immunophenotype compared to paired CD11c- B cells. Immunohistochemical and immunofluorescence staining indicated the presence of CD11c+CD19+ B cells in lymphocyte infiltration areas of the GD thyroid. Flow cytometric analysis of PB and fine-needle aspiration (FNA) samples showed that compared to PB CD11c+ B cells, CD11c+ B cells in the thyroid accumulated and further differentiated. We found that CD11c+ B cells from the PB of GD patients were induced to differentiate into autoreactive antibody-secreting cells (ASCs) capable of secreting TRAbs in vitro. Luminex liquid suspension chip detection data showed that CD11c+ B cells also secreted a variety of cytokines, including proinflammatory cytokines, anti-inflammatory cytokines, and chemokines, which might play roles in regulating the local inflammatory response and infiltration of lymphocytes in the thyroid. In addition, we performed a chemotaxis assay in a Transwell chamber to verify that CD11c+ B cells were recruited by thyroid follicular cells (TFCs) via the CXCR3-CXCL10 axis. In conclusion, our study determined that CD11c+ B cells were involved in the pathogenesis of GD in multiple ways and might represent a promising immunotherapeutic target in the future.

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Section: Resultsmentioning

confidence: 99%

CD11c+ B Cells Participate in the Pathogenesis of Graves’ Disease by Secreting Thyroid Autoantibodies and Cytokines

et al. 2022

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“…However, PD-L1 SNP (rs822339) status was not related to clinical course and anti-thyroid autoantibodies of HT in our study. Only a few studies have shown an association of PD-1 positive follicular T helper cells and natural killer cells with the pathogenesis of HT [ 29 , 30 ]. Follicular T regulatory cells, which inhibit follicular T helper cells, were also increased in HT patients, but this was not associated with anti-TPO and Tg antibody titers [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients

et al. 2021

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Background: Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Methods: A total of 189 GD patients, 234 HT patients, and 846 healthy age-and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. Results: Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment anti-TPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. Conclusion:The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

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“…PD‐1 as an immunosuppressive molecule can be expressed on the surface of T‐cells, B‐cells, natural killer (NK) cells, macrophages, DCs, innate lymphoid cells (ILCs), neutrophiles and monocytes [7]. It regulates the immune system by establishing immune tolerance to protect normal tissue [6]. However, researchers have discovered that PD‐1 has an influence on the development of numerous disorders involving immune system dysfunction, including tumours, infections and chronic inflammatory disorders.…”

Section: Pd‐1 Participates In Immune Disordersmentioning

confidence: 99%

“…CD56 + PD‐1 + NK cells in HT highly express the regulatory receptors NKG2A and NKG2C. CD56 + PD‐1 − NK cells in AITD patients showed increased synthesis of IL‐10 [6]. In children with acute febrile malaria, NK cells expressed PD‐1 and produced IL‐6; the natural killing ability of PD‐1 + NK cells was decreased, while the effect of ADCC was enhanced [51].…”

Section: Pd‐1 Participates In Immune Disordersmentioning

confidence: 99%

“…However, when the immune system is in disorder, PD‐1 exhibits abnormal expression states, which is commonly linked to immune overactivity, excessive immunosuppression and tumour escape. After more than two decades, the focus of PD‐1 research shifted from applications in autoimmune diseases (i.e., systemic lupus erythematosus, rheumatoid arthritis) and infectious diseases (i.e., HIV, HBV) [6] to antitumor applications, although it has achieved extraordinary therapeutic success in cancer, it is simultaneously associated with physiologic limitations. PD‐1 is intricately linked with systemic immunity, although its specific mechanisms are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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PD‐1: A critical player and target for immune normalization

Liu,

Zhao,

Xiao

et al. 2024

Immunology

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Immune system imbalances contribute to the pathogenesis of several different diseases, and immunotherapy shows great therapeutic efficacy against tumours and infectious diseases with immune‐mediated derivations. In recent years, molecules targeting the programmed cell death protein 1 (PD‐1) immune checkpoint have attracted much attention, and related signalling pathways have been studied clearly. At present, several inhibitors and antibodies targeting PD‐1 have been utilized as anti‐tumour therapies. However, increasing evidence indicates that PD‐1 blockade also has different degrees of adverse side effects, and these new explorations into the therapeutic safety of PD‐1 inhibitors contribute to the emerging concept that immune normalization, rather than immune enhancement, is the ultimate goal of disease treatment. In this review, we summarize recent advancements in PD‐1 research with regard to immune normalization and targeted therapy.

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Quantitative and Functional Analysis of PD-1+ NK Cells in Patients With Autoimmune Thyroid Disease

Cited by 8 publications

References 35 publications

CD11c+ B Cells Participate in the Pathogenesis of Graves’ Disease by Secreting Thyroid Autoantibodies and Cytokines

CD11c+ B Cells Participate in the Pathogenesis of Graves’ Disease by Secreting Thyroid Autoantibodies and Cytokines

Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients

PD‐1: A critical player and target for immune normalization

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