Treg cells expressing the co-inhibitory molecule TIGIT selectively inhibit pro-inflammatory Th1 and Th17 cell responses

By N. Joller, E. Lozano, Patrick R. Burkett, B. Patel, S. Xiao, Chen Zhu, J. Xia, T. G. Tan, Esen Sefik, V. Yajnik and 6 more. Immunity, 2014

877 citations recorded by the source corpus.

Summary Foxp3+ T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3+ T cells expressing the co-inhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses pro-inflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT+ Treg cells as an activated Treg subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cell cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/687c89cf6dad0b11bfc032b4fa144962c1ef5345

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In Immunology

1. Cristina Gutiérrez-Vázquez
2. F. Quintana
3. Miriam Merad
4. Rob Knight
5. Judy H. Cho
6. Y. Lee
7. S. Mazmanian

Citations in the corpus

• Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells (2016, background): “Of the ten proteins, two were proteins (OX40 and TIGIT) whose relevance for Treg cells biology has been demonstrated (Joller et al., 2014; Voo et al., 2013), seven are proteins (BATF, CCR8, CD30, IL-1R2, IL-21R, PDL-1, and PDL-2) whose expression has never been described in tumor-infiltrating Treg…”
• TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients. (2015, neutral): “TIGIT+ Tregs are highly activated, secrete the soluble effector molecule fibrinogen-like protein 2, and selectively inhibit Th1 and Th17 responses (39).”
• Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models (2017, methodology): “5ng/ml) for 4 days (12), in presence of bacterial extracts.”
• Regulation of the immune response by the aryl hydrocarbon receptor (2018, background): “It is not clear yet whether specific subpopulations of FoxP3+ Treg cells express higher levels of AhR, as recently described for TIGIT+FoxP3+ Treg cells (Joller et al., 2014), making them more susceptible to modulation by AhR agonists.”
• Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy (2019, background): “Interestingly, Tregs strongly expressed the co-inhibitory receptor TIGIT, which was shown to inhibit pathogenic Th1 and Th17 responses during murine intestinal inflammation (Joller et al., 2014), as well as the co-stimulatory receptor CD27, recently suggested as an important repressor of Th17 functi”