ID2 and ID3 are indispensable for Th1 cell differentiation during influenza virus infection in mice.

Abstract

Antigen-specific Th1 cells could be a passage to the infection sites during infection to execute effector functions, such as help CD8+ T cells to localize in these sites by secretion of anti-viral cytokines-IFN-γ or direct cytotoxicity of antigen-bearing cells. However, the molecular components that modulate Th1 cell differentiation and function in response to viral infection remain incompletely understood. Here, we reported that both inhibitor of DNA binding 3(Id3) protein and inhibitor of DNA binding 2(Id2) protein promoted Th1 cell differentiation. Depletion of Id3 or Id2 led to severe defect of Th1 cell differentiation during influenza virus infection. Whereas depletion of both Id3 and Id2 in CD4+ T cells restrained Th1 cell differentiation to a greater extent, indicating that Id3 and Id2 nonredundantly regulate Th1 cell differentiation. Moreover, deletion of E-proteins, the antagonists of Id proteins, greatly enhanced Th1 cell differentiation. Mechanistic study indicated that E-proteins suppressed Th1 cell differentiation by directly binding to the regulatory elements of Th1 cell master regulator T-bet and regulate T-bet expression. Thus, our findings identified Id-protein's importance for Th1 cells and clarified the nonredundant role of Id3 and Id2 in regulating Th1 cell differentiation, providing novel insight that Id3-Id2-E protein axis are essential for Th1 cell polarization.

• Authors: Xiaojuan Han, Hongtao Liu, Huarong Huang, Xinyuan Liu, Baoqian Jia, George Fu Gao, Fuping Zhang
• Journal: European journal of immunology (Eur J Immunol) Vol. 49 Issue 3 Pg. 476-489 (03 2019) ISSN: 1521-4141 [Electronic] Germany
• PMID: 30578645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Idb2 protein, mouse
• Inhibitor of Differentiation Protein 2
• Inhibitor of Differentiation Proteins
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Idb3 protein, mouse

Topics

• Animals
• Basic Helix-Loop-Helix Transcription Factors (genetics, immunology, metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• CD8-Positive T-Lymphocytes (immunology, metabolism, virology)
• Cell Differentiation (genetics, immunology)
• Gene Expression Regulation (immunology)
• Inhibitor of Differentiation Protein 2 (genetics, immunology, metabolism)
• Inhibitor of Differentiation Proteins (genetics, immunology, metabolism)
• Mice, Knockout
• Mice, Transgenic
• Orthomyxoviridae (immunology, physiology)
• Orthomyxoviridae Infections (genetics, immunology, virology)
• Regulatory Elements, Transcriptional (genetics)
• T-Box Domain Proteins (genetics, immunology, metabolism)
• Th1 Cells (immunology, metabolism, virology)