Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3
            <sup>high</sup>
            regulatory T cells in humans

Miyara, Makoto; Chader, Driss; Sage, Édouard; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Bouvry, Diane; Claër, Laetitia; Hingorani, Ravi; Balderas, Robert; Rohrer, Jurg; Warner, Noel L.; Chapelier, Alain; Valeyre, Dominique; Kannagi, Reiji; Sakaguchi, Shimon; Amoura, Zahir; Gorochov, Guy

doi:10.1073/pnas.1508224112

Cited by 134 publications

(131 citation statements)

References 35 publications

(66 reference statements)

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“…In fact, some overlap with known loci for psoriasis and inflammatory bowel disease (7-9), findings consistent with the finding of multiple aberrations in adaptive immunity in patients with sarcoidosis (10)(11)(12). Others have previously demonstrated the significance of reduced levels of nuclear factor-kB (NF-kB)/P65 to sarcoidosis disease severity (12), as well as dysregulation within IL-12 and IL-23 pathways within cutaneous sarcoidosis specimens, using microarray analysis (13).…”

supporting

confidence: 58%

Solving the Conundrum: Immunogenetics of Sarcoidosis

Kaminski

Drake²

2015

Am J Respir Crit Care Med

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conducted during very brief periods (only 2 h of respiratory electrodialysis), and that further complications may arise when performing the technique over clinically meaningful periods. Moreover, the technical setup is complex and will need to be as safe as possible before it can be deployed in human trials. ConclusionsDuring the last decades, we have learned that the iatrogenic effects of invasive mechanical ventilation may negatively influence outcomes. Minimally invasive extracorporeal lung assist devices markedly reducing the need for alveolar ventilation would or could play a pivotal role in mitigating these negative influences.The innovative approach of Zanella and colleagues opens the possibility of ensuring sufficient CO 2 removal with a less-invasive way of using positive pressure ventilation than the current standard, or by eliminating invasive mechanical ventilation altogether. Doubling the amount of extracorporeal CO 2 removal would allow a considerable decrease in invasiveness by enabling lower flow rates and vascular access with smaller cannulae. Moreover, it offers the opportunity to widely apply and evaluate the concept of ultraprotective ventilation to reduce VILI, as well as a potential alternative to invasive mechanical ventilation for the support of hypercapnic respiratory failure. If the technique of Zanella and colleagues could be successfully transferred to the clinical setting, it might mark a quantum jump in the treatment of respiratory failure of different etiologies. n

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supporting

confidence: 58%

Solving the Conundrum: Immunogenetics of Sarcoidosis

Kaminski

Drake²

2015

Am J Respir Crit Care Med

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“…6B). In comparison to eTreg cells, cTfr cells had reduced expression of Foxp3, and the previously identified eTreg marker CD15s (35) (Fig. 6C).…”

Section: Il-2 Antagonizes the Formation And Maintenance Of Cd25 − Tfrmentioning

confidence: 63%

A distinct subpopulation of CD25⁻T-follicular regulatory cells localizes in the germinal centers

Wing

Kitagawa

Locci

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differentiation is inhibited by IL-2, regulatory T (Treg) cell differentiation and survival depend on it. Here, we describe a CD25− subpopulation within both murine and human PD1+CXCR5+Foxp3+ Tfr cells. It is preferentially located in the GC and can be clearly differentiated from CD25+ non–GC-Tfr, Tfh, and effector Treg (eTreg) cells by the expression of a wide range of molecules. In comparison to CD25+ Tfr and eTreg cells, CD25− Tfr cells partially down-regulate IL-2–dependent canonical Treg features, but retain suppressive function, while simultaneously up-regulating genes associated with Tfh and GC-Tfh cells. We suggest that, similar to Tfh cells, Tfr cells follow a differentiation pathway generating a mature GC-localized subpopulation, CD25− Tfr cells.

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“…Thus, there could be positive correlations between Foxp3 + TILs and PD-L1 expression on either IC or TC. A recent study reported that Foxp3 + T reg cells are divided into specific subsets including the highly differentiated and most suppressive Foxp3 + high T reg cells41. We do not know the exact status of T reg cells in previous reports including ours, because previous studies typically used Foxp3 as a representative marker of T reg cells.…”

Section: Discussionmentioning

confidence: 76%

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

Kim

Hong

et al. 2016

Sci Rep

221

169

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To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.

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Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3 ^high regulatory T cells in humans

Cited by 134 publications

References 35 publications

Solving the Conundrum: Immunogenetics of Sarcoidosis

Solving the Conundrum: Immunogenetics of Sarcoidosis

A distinct subpopulation of CD25⁻T-follicular regulatory cells localizes in the germinal centers

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

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Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3 high regulatory T cells in humans

Cited by 134 publications

References 35 publications

Solving the Conundrum: Immunogenetics of Sarcoidosis

Solving the Conundrum: Immunogenetics of Sarcoidosis

A distinct subpopulation of CD25−T-follicular regulatory cells localizes in the germinal centers

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients

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Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3 ^high regulatory T cells in humans

A distinct subpopulation of CD25⁻T-follicular regulatory cells localizes in the germinal centers