Hsin-Jung Joyce Wu, PhD

Associate Professor, Immunobiology
Associate Professor, BIO5 Institute
Research Scientist, Arizona Center on Aging
Research Scientist, Arthritis Center-Research
Research Scientist, Cancer Center Division

Hsin-Jung Joyce Wu received her PhD degree from the University of Kentucky, studying B cell signaling. For her post-doctoral training, Joyce joined the lab of Diane Mathis and Christophe Benoist at Harvard University, where she investigated the roles of gut microbiota in autoimmune diseases. She is a faculty member of the University of Arizona since 2011. Joyce was promoted to Associate Professor with tenure in Spring 2017.

Research Interests: 

My laboratory works on our long-standing interest: the role of microbes in autoimmune disease with a unique focus, mucosal immunity. Imbalance of gut microbiota can lead to many diseases including those located systemically (outside the gut; e.g. rheumatoid arthritis, type 1 diabetes, lupus, etc.). Accordingly, the big question that my laboratory is focusing on is how gut microbiota remotely exert systemic effects. We have established a new system to examine commensal-host interactions by manipulating the status of the commensal, segmented filamentous bacteria (SFB), in the K/BxN arthritis model housed in a specific pathogen free (SPF) facility. We also developed a state-of-the-art photoconverting technique to track single cell migration between gut and systemic tissues. With these systems, we were able to show that SFB remotely trigger systemic autoimmune arthritis by driving the induction and egression of gut T follicular helper (Tfh) cells.

Lung complications are common and a major cause of death in patients with rheumatoid arthritis (RA) and we are very interested in understanding how do microbiota residing in the gut affect autoimmune disease in the lung. A long-standing question in the host-microbe field is, “how are microbes involved in the development of autoimmunity?” Although molecular mimicry is the dominant theory, we discovered that commensal SFB actually trigger autoimmunity in lung by a different mechanism, by inducing dual TCR-expressing Th17 cells derived from the gut-lung axis. SFB selectively expand autoimmune T cells co-expressing SFB-specific TCRs in addition to their auto-reactive TCRs. This additional SFB-specific TCR provides a proliferative advantage for autoimmune Th17 cells in SFB+ hosts. We are now using single cell TCR analysis to unbiasedly determine whether microbiota promote autoimmunity by skewing the dual TCR repertoire. To further identify the gut-lung axis related autoimmunity, we have lung function (flexiVent) data suggesting that the middle-aged K/BxN lung displays increased total respiratory resistance similar to RA patients.   

For translational purposes, we are actively pursuing a project studying human commensals isolated from spondyloarthritis (SpA) patients. Recently, we reported that commensals from human SpA patients cause augmentation of autoimmune arthritis, and we are hoping to further understand the mechanisms behind this disease phenotype. With our strong interest, knowledge, and tools in mucosal immunity, including lung and gut immunity, and also through our collaborative efforts, my lab aims to continually contribute to this exciting field by elucidating the crucial mechanisms through which gut microbiota affect non-gut diseases in the joints and lung.

Recent Publications

2019

Sprouse, M. L., N. A. Bates, K. M. Felix, and H-J. Joyce Wu, "Impact of gut microbiota on gut-distal autoimmunity: a focus on T cells.", Immunology, vol. 156, issue 4, pp. 305-318, 2019 Apr. PMCID: PMC6418419  PMID: 30560993

2018

Felix, K. M., I. A. Jaimez, T-V. V. Nguyen, H. Ma, W. A. Raslan, C. N. Klinger, K. P. Doyle, and H-J. J. Wu, "Gut Microbiota Contributes to Resistance Against Pneumococcal Pneumonia in Immunodeficient Rag Mice.", Front Cell Infect Microbiol, vol. 8, pp. 118, 2018. PMCID: PMC5932343  PMID: 29755958

2017

Viladomiu, M., C. Kivolowitz, A. Abdulhamid, B. Dogan, D. Victorio, J. G. Castellanos, V. Woo, F. Teng, N. L. Tran, A. Sczesnak, et al., "IgA-coated E. coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation.", Sci Transl Med, vol. 9, issue 376, 2017 Feb 08. PMID: 28179509
Naskar, D., F. Teng, K. M. Felix, P. C Bradley, and H-J. Joyce Wu, "Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses.", J Immunol, vol. 198, issue 5, pp. 1855-1864, 2017 Mar 01. PMCID: PMC5324833  PMID: 28130500
C Bradley, P., F. Teng, K. M. Felix, T. Sano, D. Naskar, K. E. Block, H. Huang, K. S. Knox, D. R. Littman, and H-J. Joyce Wu, "Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs.", Cell Host Microbe, vol. 22, issue 5, pp. 697-704.e4, 2017 11 08. PMCID: PMC5749641  PMID: 29120746
Felix, K. M., S. Tahsin, and H-J. Joyce Wu, "Host-microbiota interplay in mediating immune disorders.", Ann N Y Acad Sci, 2017 Oct 06. PMCID: PMC5889363  PMID: 28984367

2016

Teng, F., C. N. Klinger, K. M. Felix, P. C Bradley, E. Wu, N. L. Tran, Y. Umesaki, and H-J. Joyce Wu, "Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer's Patch T Follicular Helper Cells.", Immunity, vol. 44, issue 4, pp. 875-88, 2016 Apr 19. PMID: 27096318
Tan, T. Guan, E. Sefik, N. Geva-Zatorsky, L. Kua, D. Naskar, F. Teng, L. Pasman, A. Ortiz-Lopez, R. Jupp, H-J. Joyce Wu, et al., "Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice.", Proc Natl Acad Sci U S A, vol. 113, issue 50, pp. E8141-E8150, 2016 Dec 13. PMCID: PMC5167147  PMID: 27911839

2012

Wu, H-J., and E. Wu, "The role of gut microbiota in immune homeostasis and autoimmunity.", Gut Microbes, vol. 3, issue 1, pp. 4-14, 2012 Jan-Feb. PMCID: PMC3337124  PMID: 22356853

2011

Kriegel, M. A., E. Sefik, J. A. Hill, H-J. Wu, C. Benoist, and D. Mathis, "Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice.", Proc Natl Acad Sci U S A, vol. 108, issue 28, pp. 11548-53, 2011 Jul 12. PMCID: PMC3136249  PMID: 21709219