Quantitative and functional analysis of CD69+ NKG2D+ T regulatory cells in healthy subjects

Vitales-Noyola, Marlen; Doníz-Padilla, Lesly; Álvarez-Quiroga, Crisol; Monsiváis‐Urenda, Adriana; Portillo-Salazar, Haydée; González‐Amaro, Roberto

doi:10.1016/j.humimm.2015.06.003

Cited by 17 publications

(23 citation statements)

References 37 publications

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“…Thus, the aim of this study was to analyze the levels and function of CD69 + Treg cells in patients with PD. In this regard, we and others have recently described that although the frequency of these cells is low in peripheral blood, they seem to exert a relevant immune regulatory function, inhibiting the activation and proliferation of effector lymphocytes .…”

Section: Discussionmentioning

confidence: 89%

“…In this regard, we have recently detected that patients with autoimmune thyroiditis show increased levels of CD69 + NKG2D + IL-10 + Treg lymphocytes in their peripheral blood and thyroid tissue, with a defective immunosuppressive function (23). Furthermore, we have observed that patients with generalized autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis, also show abnormalities in the number and function of CD69 + Treg lymphocytes (14). In addition, it has been reported that patients with hepatocellular carcinoma show increased levels of these CD69 + Treg cells, which exhibit an important immune suppressive function in vitro (24).…”

Section: Introductionmentioning

confidence: 98%

“…Since different data indicated the possible involvement of Treg cells in the pathogenesis of PD, several groups have studied the number, function and effect of these cells in this condition (15)(16)(17)(18)(19)(20)(21)(22). However, most of these studies have been focused to CD4 + Foxp3 + CD25 + Treg cells, and several of these works corresponded to animal models of PD (12)(13)(14)(15)(16)(17)(18)(19). Thus, the possible contribution of Treg cell subsets different from those described by Sakaguchi (7,8) to the pathogenesis of PD has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease

Vitales-Noyola

Martínez-Martínez

Loyola-Rodríguez

et al. 2016

J Oral Pathology Medicine

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease

Vitales-Noyola

Martínez-Martínez

Loyola-Rodríguez

et al. 2016

J Oral Pathology Medicine

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“…The role of CD69 as a negative regulator of the immune system has remained a controversial issue during the last years (23). However, very recent studies by independent groups show that CD69 plays a crucial role in the suppressor function of mouse and human Treg cells as well as in the generation of in vitro-induced Treg cells (12,16,(24)(25)(26). Nevertheless, the specific role of the C-type lectin in the development of Treg cells in the thymus remains elusive.…”

Section: Discussionmentioning

confidence: 99%

“…CD69 deficiency in mice compromises T cell-induced colitis and the establishment of oral tolerance after antigen challenge in vivo (24), and CD69 ϩ pTreg cells are essential for the prevention of asthmatic reactions to harmless antigens (12). Furthermore, a subset of CD69 ϩ Treg cells in the blood of healthy human donors seems to have a relevant immune-regulatory role (25).…”

Section: Discussionmentioning

confidence: 99%

Thymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression

Sánchez-Díaz

Blanco-Domínguez

Lasarte

et al. 2017

Molecular and Cellular Biology

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Thymus-derived regulatory T (tTreg) cells are key to preventing autoimmune diseases, but the mechanisms involved in their development remain unsolved. Here, we show that the C-type lectin receptor CD69 controls tTreg cell development and peripheral Treg cell homeostasis through the regulation of BIC/microRNA 155 (miR-155) and its target, suppressor of cytokine signaling 1 (SOCS-1). Using Foxp3-mRFP/cd69 ϩ/Ϫ or Foxp3-mRFP/cd69 Ϫ/Ϫ reporter mice and short hairpin RNA (shRNA)-mediated silencing and miR-155 transfection approaches, we found that CD69 deficiency impaired the signal transducer and activator of transcription 5 (STAT5) pathway in Foxp3 ϩ cells. This results in BIC/miR-155 inhibition, increased SOCS-1 expression, and severely impaired tTreg cell development in embryos, adults, and Rag2 Ϫ/Ϫ ␥c Ϫ/Ϫ hematopoietic chimeras reconstituted with cd69 Ϫ/Ϫ stem cells. Accordingly, mirn155 Ϫ/Ϫ mice have an impaired development of CD69 ϩ tTreg cells and overexpression of the miR-155-induced CD69 pathway, suggesting that both molecules might be concomitantly activated in a positive-feedback loop. Moreover, in vitro-inducible CD25 ϩ Treg (iTreg) cell development is inhibited in Il2r␥ Ϫ/Ϫ /cd69 Ϫ/Ϫ mice. Our data highlight the contribution of CD69 as a nonredundant key regulator of BIC/miR-155-dependent Treg cell development and homeostasis.

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Levels of regulatory T cells CD69+NKG2D+IL-10+ are increased in patients with autoimmune thyroid disorders

et al. 2015

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Regulatory T (Treg) cells play an important role in the pathogenesis of autoimmune thyroid disorders (AITD). New subsets of CD4(+)CD69(+) and CD4(+)NKG2D(+) T lymphocytes that behave as regulatory cells have been recently reported. The role of these immunoregulatory lymphocytes has not been previously explored in AITD. We analyzed by multi-parametric flow cytometry different Treg cell subsets in peripheral blood from 32 patients with AITD and 19 controls, and in thyroid tissue from seven patients. The suppressive activity was measured by an assay of inhibition of lymphocyte activation. We found a significant increased percentage of CD4(+)CD69(+)IL-10(+), CD4(+)CD69(+)NKG2D(+), and CD4(+)CD69(+)IL-10(+)NKG2D(+) cells, in peripheral blood from GD patients compared to controls. The increase in CD4(+)CD69(+)IL-10(+) and CD4(+)CD69(+)IL-10(+)NKG2D(+) T cells was especially remarkable in patients with active Graves' ophthalmopathy (GO), and a significant positive correlation between GO activity and CD4(+)CD69(+)IL-10(+) or CD4(+)CD69(+)IL-10(+)NKG2D(+) cells was also found. In addition, these cells were increased in patients with a more severe and/or prolonged disease. Thyroid from AITD patients showed an increased proportion of CD69(+) regulatory T cells subpopulations compared to autologous peripheral blood. The presence of CD69(+), NKG2D(+), and IL-10(+) cells was confirmed by immunofluorescence microscopy. In vitro functional assays showed that CD69(+) Treg cells exerted an important suppressive effect on the activation of T effector cells in controls, but not in AITD patients. Our findings suggest that the levels of CD69(+) regulatory lymphocytes are increased in AITD patients, but they are apparently unable to down-modulate the autoimmune response and tissue damage.

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Quantitative and functional analysis of CD69+ NKG2D+ T regulatory cells in healthy subjects

Cited by 17 publications

References 37 publications

Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease

Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease

Thymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression

Levels of regulatory T cells CD69+NKG2D+IL-10+ are increased in patients with autoimmune thyroid disorders

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Quantitative and functional analysis of CD69+ NKG2D+ T regulatory cells in healthy subjects

Cited by 17 publications

References 37 publications

Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease

Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease

Thymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression

Levels of regulatory T cells CD69+NKG2D+IL-10+ are increased in patients with autoimmune thyroid disorders

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Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease

Quantitative and functional analysis of CD69⁺ T regulatory lymphocytes in patients with periodontal disease