Plasmacytoid Dendritic Cells in Patients With Autoimmune Thyroid Disease

Leskelä, Susanna; Rodríguez-Muñoz, Ana; Fuente, Hortensia de la; Figueroa-Vega, Nicté; Bonay, Pedro; Martı́n, Pilar; Serrano, A.; Sánchez-Madrid, Francisco; González‐Amaro, Roberto; Marazuela, Mónica

doi:10.1210/jc.2013-1273

Cited by 36 publications

(45 citation statements)

References 39 publications

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“…22 sILT3 is also elevated in serum of patients with melanoma, colorectal cancer, and pancreatic carcinoma 21,22 In contrast, ILT3 expression is decreased on DCs of patients with systemic lupus erythematosus (SLE) and autoimmune thyroid disease, where, in contrast to cancer, the immune system is overactivated 15,39 and ILT3 was also reported to be decreased on circulating monocytes of patients with multiple sclerosis. 16 In line with these results, we found elevated sILT3 levels and a higher percentage of ILT3…”

Section: Ilt3mentioning

confidence: 99%

“…11,12 ILT3 expression marks tolerogenic DCs and has been reported to be elevated in APCs of cancer patients 13,14 and decreased in autoimmune diseases. 15,16 ILT3 is believed to signal via its immunoreceptor tyrosine-based inhibitory motifs (ITIMs). These motifs are known to inhibit NF-kB activation and transcription of costimulatory molecules and thereby render the cell tolerogenic.…”

Section: Introductionmentioning

confidence: 99%

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Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

et al. 2015

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Myeloid-derived suppressor cells (MDSCs) play an important role in immune suppression and accumulate under pathologic conditions such as cancer and chronic inflammation. They comprise a heterogeneous population of immature myeloid cells that exert their immunosuppressive function via a variety of mechanisms. Immunoglobulin-like transcript 3 (ILT3) is a receptor containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) that can be expressed on antigen-presenting cells and is an important regulator of dendritic cell tolerance. ILT3 exists in a membrane-bound and a soluble form and can interact with a yet unidentified ligand on T cells and thereby induce T-cell anergy, regulatory T cells, or T suppressor cells. In this study, we analyzed freshly isolated peripheral blood mononuclear cells (PBMCs) of 105 patients with non-small cell lung cancer and 20 healthy controls and demonstrated for the first time that ILT3 is expressed on MDSCs. We show that increased levels of circulating MDSCs correlate with reduced survival. On the basis of ILT3 cell surface expression, an ILT3 low and ILT3 high population of polymorphonuclear (PMN)-MDSCs could be distinguished. Interestingly, in line with the immunosuppressive function of ILT3 on dendritic cells, patients with an increased proportion of PMN-MDSCs and an increased fraction of the ILT3 high subset had a shorter median survival than patients with elevated PMN-MDSC and a smaller ILT3 high fraction. No correlation between the ILT3 high subset and other immune variables was found. ILT3 expressed on MDSCs might reflect a previously unknown mechanism by which this cell population induces immune suppression and could therefore be an attractive target for immune intervention.

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Section: Ilt3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

et al. 2015

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“…Similarly, sera from patients with active systemic lupus erythematosus showed increased IDO activity, as determined by a higher kynurenine/tryptophan liquid chromatography ratio (40), and in patients with active Crohn's disease, abundant IDO positive dendritic cells are found lining the ulcerative fissures that are scattered throughout the intestinal mucosa (41). By contrast, diminished numbers of IDO positive plasmacytoid dendritic cells have been reported in patients with autoimmune thyroid disease (42). Therefore, both decreased and increased IDO function has been associated with autoimmune diseases.…”

Section: Discussionmentioning

confidence: 95%

“…The different IDO levels reported in autoimmunity could also be attributed to different disease stage and severity. For example, in patients with long-standing Hashimoto thyroiditis, where these counter-regulatory mechanisms are likely exhausted, the expression of IDO is significantly diminished in plasmacytoid dendritic cells (42).…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Sharma

Dalmazi

Caturegli

2016

Thyroid

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Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2 h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. Conclusions: This study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2 h4 mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade.

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“…The evaluation of peripheral blood DC subpopulation in comparison to thyroid gland [33] It was claimed that molecules involved in chronic inflammation can also have a considerable function in tumor induction and development. DCs have also been proposed to participate in the development of thyroid cancer.…”

Section: Dendritic Cells (Dcs)mentioning

confidence: 99%

Thyroid Autoimmunity and Cancer

Felicetti¹,

Catalano²,

Fortunati³

2017

Frontiers of Hormone Research

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Cancer and autoimmune diseases are often associated in the same individual. The functional link between immune system and cancer development is only partially known. Even though the immune system can control the development of cancer through immune surveillance, cancer cell itself can escape immune surveillance. Actually, it is debated whether autoimmune diseases have to be regarded as cancer cause or its consequence.In particular, autoimmune thyroiditis and thyroid cancer (in particular, papillary thyroid cancer) are a fascinating model of this complex relationship. In the present review, we describe what has been reported by now in literature about autoimmune thyroiditis and papillary thyroid cancer, and on the basis of available data, we try to clarify the present knowledge.

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Plasmacytoid Dendritic Cells in Patients With Autoimmune Thyroid Disease

Abstract: The diminished number of pDCs in the peripheral blood from AITD patients as well as their abnormal phenotype could contribute significantly to the pathogenesis.

Cited by 36 publications

References 39 publications

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

Thyroid Autoimmunity and Cancer

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