Xin Chen

All Publications

• Embracing Interpersonal Variability of Microbiome in Precision Medicine PHENOMICS Zhou, X., Chen, X., Davis, M. M., Snyder, M. P. 2025

  View details for DOI 10.1007/s43657-024-00201-w

  View details for Web of Science ID 001426158600001

• Embracing Interpersonal Variability of Microbiome in Precision Medicine. Phenomics (Cham, Switzerland) Zhou, X., Chen, X., Davis, M. M., Snyder, M. P. 2025; 5 (1): 8-13

  View details for DOI 10.1007/s43657-024-00201-w

  View details for PubMedID 40313605

  View details for PubMedCentralID PMC12040794

• Differential roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses. Nature immunology Chen, X., Ghanizada, M., Mallajosyula, V., Sola, E., Capasso, R., Kathuria, K. R., Davis, M. M. 2025

  Abstract

  Here we analyzed the relative contributions of CD4+ regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8+ regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4+ and CD8+ regulatory T cells. Using CRISPR-Cas9 gene editing, we were able to achieve a reduction of ~90-95% in the expression of these genes. FOXP3 knockout in tonsil T cells led to production of antibodies against a variety of autoantigens and increased the affinity of influenza-specific antibodies. By contrast, GZMB knockout resulted in an increase in follicular helper T cells, consistent with the ablation of CD8+ regulatory T cells observed in mouse models, and a marked expansion of autoreactive CD8+ and CD4+ T cells. These findings highlight the distinct yet complementary roles of CD8+ and CD4+ regulatory T cells in regulating cellular and humoral responses to prevent autoimmunity.

  View details for DOI 10.1038/s41590-024-02062-x

  View details for PubMedID 39806065

  View details for PubMedCentralID 6738855

• Organophosphate ester flame retardant chemicals and maternal depression during pregnancy Environmental Research Hernandez-Castro, I., Eckel, S. P., Howe, C. G., Aung, M. T., Kannan, K., Robinson, M., Foley, H. B., Yang, T., Vigil, M. J., Chen, X., Grubbs, B., Al-Marayati, L., Toledo-Corral, C. M., Habre, R., Dunton, G. F., Farzan, S. F., Morales, S., Breton, C. V., Bastain, T. M. 2024

  View details for DOI 10.1016/j.envres.2024.119581

• RNA-seq based transcriptome analysis of murine macrophages RAW264.7 treated with multi-herbal extracts reveals immunomodulatory potential and mechanism FOOD AND AGRICULTURAL IMMUNOLOGY Jin, M., Chen, X., Wu, Q., Guo, Z., Zhang, R., Jiang, Y., Li, X., Zhang, L., Wang, Y., Zhou, X. 2023; 34 (1): 21-35

  View details for DOI 10.1080/09540105.2023.2192443

  View details for Web of Science ID 000960511300001

• RNA-seq analysis reveals an immunomodulatory peptide from highland barley activating RAW264.7 macrophages via TNF/NF-κB signaling pathway. Functional & integrative genomics Liu, Y., Chen, X., Yang, J. Y., Guo, Z. J., Wu, Q., Zhang, L. D., Zhou, X. W. 2023; 23 (3): 253

  Abstract

  Highland barley (HB) is an important cereal crop distributed in the plateau region. Bioactive peptides (BAPs) derived from cereal proteins have shown biological functions. However, the knowledge of highland barley peptide (HBP) is limited. This study aims to explore the immunomodulatory activity of HBP and the relationship between immunomodulatory activity and related gene expression through RNA-seq. Firstly, HBP is isolated from protease hydrolysates of HB protein, yielding 12.04% of crude HB protein. The molecular weight of HBP is about 1702 Da analyzed by gel filtration chromatography, and HBP has a specific amino acid sequence as Gln-Pro-Gln-Gln-Pro-Phe-Pro-Gln (QPQPFPQ) analyzed by LC-MS. Besides, HBP contains 42.20% hydrophobic amino acids and 10.86% basic amino acids. Next, the immunomodulatory activity of HBP in vitro shows that HBP enhances the phagocytosis of RAW264.7 macrophages, promotes nitric oxide (NO) production and the mRNA expression of pro-inflammatory genes including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and inducible nitric oxide synthase (iNOS), and decreases the mRNA expression of anti-inflammatory gene, transforming growth factor β1 (TGF-β1). RNA-seq analysis reveals TNF and nuclear factor kappa B (NF-κB) pathways are upregulated, and RT-qPCR is performed to verify RNA-seq analysis. In conclusion, HBP activates RAW264.7 macrophages via TNF/NF-κB signaling pathway. HBP, as a significant immunomodulatory peptide, might be a promising resource for future functional foods.

  View details for DOI 10.1007/s10142-023-01180-3

  View details for PubMedID 37488420

  View details for PubMedCentralID 7295866

• A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2. Nature materials Yin, Q., Luo, W., Mallajosyula, V., Bo, Y., Guo, J., Xie, J., Sun, M., Verma, R., Li, C., Constantz, C. M., Wagar, L. E., Li, J., Sola, E., Gupta, N., Wang, C., Kask, O., Chen, X., Yuan, X., Wu, N. C., Rao, J., Chien, Y., Cheng, J., Pulendran, B., Davis, M. M. 2023

  Abstract

  The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

  View details for DOI 10.1038/s41563-022-01464-2

  View details for PubMedID 36717665

• N-Glycosylated Ganoderma lucidum immunomodulatory protein improved anti-inflammatory activity via inhibition of the p38 MAPK pathway. Food & function Li, Q. Z., Chen, X., Mao, P. W., Jin, M. Y., Wu, Q., Zhou, X. W. 2021; 12 (8): 3393-3404

  Abstract

  The global health emergency generated by coronavirus disease-2019 has prompted the search for immunomodulatory agents. There are many potential natural products for drug discovery and development to tackle this disease. One of these candidates is the Ganoderma lucidum fungal immunomodulatory protein (FIP-glu). In the present study, we clarify the influences of N-linked glycans on the improvement of anti-inflammatory activity and the potential mechanisms of action. Four proteins, including FIP-glu (WT) and its mutants N31S, T36N and N31S/T36N, were successfully expressed in P. pastoris, of which T36N and N31S/T36N were glycoproteins. After treatment with peptide-N-glycosidase F, the results of SDS-PAGE and Western blot showed that the glycan moiety was removed completely, indicating that the glycan moiety was N-linked. This was also demonstrated by UPLC-qTOF-MS. The cytotoxicity assay showed that N-linked glycans decreased the cytotoxicity of WT; while, the RT-qPCR assay showed that N-glycosylated WT regulated the mRNA expression of IL-6 and TGF-β1. The Western blot results showed that N-glycosylated WT reduced the phosphorylation level of p38 MAPK. In conclusion, our findings revealed a novel mechanism by which N-glycosylation of FIP-glu improved its anti-inflammatory activity through the regulation of the expression of inflammatory cytokines in RAW264.7 via inhibition of p38 MAPK phosphorylation. It was proved that N-glycosylation significantly improved the functional properties of FIP-glu, providing theoretical and technical support for expanding the application of FIPs in the food and pharmaceutical industries.

  View details for DOI 10.1039/d1fo00178g

  View details for PubMedID 33900328

• The Impact of SARS-CoV-2 on the Human Immune System and Microbiome INFECTIOUS MICROBES & DISEASES Wang, C., Zhou, X., Wang, M., Chen, X. 2021; 3 (1): 14-21

  View details for DOI 10.1097/IM9.0000000000000045

  View details for Web of Science ID 000730626200004

• The Impact of SARS-CoV-2 on the Human Immune System and Microbiome. Infectious microbes & diseases Wang, C., Zhou, X., Wang, M., Chen, X. 2021; 3 (1): 14-21

  Abstract

  A recent outbreak of coronavirus disease 2019 (COVID-19) caused by the single-stranded enveloped RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic, after it was first reported in Wuhan in December 2019. SARS-CoV-2 is an emerging virus, and little is known about the basic characteristics of this pathogen, the underlying mechanism of infection, and the potential treatments. The immune system has been known to be actively involved in viral infections. To facilitate the development of COVID-19 treatments, the understanding of immune regulation by this viral infection is urgently needed. This review describes the mechanisms of immune system involvement in viral infections and provides an overview of the dysregulation of immune responses in COVID-19 patients in recent studies. Furthermore, we emphasize the role of gut microbiota in regulating immunity and summarized the impact of SARS-CoV-2 infection on the composition of the microbiome. Overall, this review provides insights for understanding and developing preventive and therapeutic strategies by regulating the immune system and microbiota.

  View details for DOI 10.1097/IM9.0000000000000045

  View details for PubMedID 38630064

  View details for PubMedCentralID PMC8011344