Apolipoprotein E mediates cell resistance to influenza virus infection.

Viruses exploit host cell machinery to support their replication. Defining the cellular proteins and processes required for a virus during infection is crucial to understanding the mechanisms of virally induced disease and designing host-directed therapeutics. Here, we perform a genome-wide CRISPR-Cas9-based screening in lung epithelial cells infected with the PR/8/NS1-GFP virus and use GFP cell as a unique screening marker to identify host factors that inhibit influenza A virus (IAV) infection.

The Crohn Disease-associated ATG16L1 polymorphism regulates inflammatory responses by modulating TLR- and NLR-mediated signaling.

The mechanisms by which the ATG16L1 polymorphism affects cell function and causes an increased risk for the development of Crohn disease remain incompletely understood. Here we report that healthy individuals and mice bearing this polymorphism, even as heterozygotes, manifest enhanced TLR, and NLR cytokine and chemokine responses due to increased activation of NFKB. We elucidated the mechanism of the NFKB abnormality and found that in the ATG16L1 cell, there is enhanced polyubiquitination of TRAF6 or RIPK2 resulting from the accumulation of SQSTM1/p62.

IBD-Associated Atg16L1T300A Polymorphism Regulates Commensal Microbiota of the Intestine.

The development of inflammatory bowel disease (IBD) is driven by the interaction among host genetics, microbiota, and the immune system of the entire digestive tract. Atg16L1T300A polymorphism is a genetic factor that confers increased risk for the pathogenesis of Crohn's disease. However, the exact contributions of Atg16L1T300A to intestinal mucosal homeostasis are not well understood.

E-protein regulatory network links TCR signaling to effector Treg cell differentiation.

T cell antigen receptor (TCR) signaling is essential for the differentiation and maintenance of effector regulatory T (Treg) cells. However, the contribution of individual TCR-dependent genes in Treg cells to the maintenance of immunotolerance remains largely unknown. Here we demonstrate that Treg cells lacking E protein undergo further differentiation into effector cells that exhibit high expression of effector Treg signature genes, including IRF4, ICOS, CD103, KLRG-1, and RORγt.

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

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.

CD8 T Cell Immune Response in Immunocompetent Mice during Zika Virus Infection.

Zika virus (ZIKV) infection causees neurologic complications, including Guillain-Barré syndrome in adults and central nervous system (CNS) abnormalities in fetuses. We investigated the immune response, especially the CD8 T cell response in C57BL/6 (B6) wild-type (WT) mice, during ZIKV infection. We found that a robust CD8 T cell response was elicited, major histocompatibility complex class I-restricted CD8 T cell epitopes were identified, a tetramer that recognizes ZIKV-specific CD8 T cells was developed, and virus-specific memory CD8 T cells were generated in these mice.