Lei Jin, PhD, MSc

Lei Jin, PhD, MSc
Assistant Professor of Medicine

Email: Lei.Jin@medicine.ufl.edu
Phone: 352.294.8495

Degree/Program

Institution

Field/Specialty

BScFudan University, ChinaBiophysics
MScFudan University, ChinaHuman Genetics
PhDTufts UniversityGenetics
Postdoctoral FellowNational Jewish Health/University of Colorado DenverImmunology

Research Interests

Dr. Jin’s lab researches lung dendritic cells (DCs) and human STING (stimulator of interferon genes). We use the mouse to model human diseases to dissect the in vivo mechanisms. We use primary human samples to confirm animal studies. Last, we are committed to translational research that can result in curative care.

Maintain lung tolerance by the lung IFNAR1+TNFR2+ cDC2 (iR2D2) population.
The lung is a tolerogenic organ. Loss of lung mucosal tolerance causes chronic inflammatory lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and asthma. Over 36 million people in the U.S suffer from asthma or COPD. Together, they are the 4th leading cause of death in the U.S. Current treatments for COPD or asthma do not repair the underlying impaired lung mucosal tolerance. Patients relapse after the treatments stop. Lung DCs sense environmental cues and direct lung immune responses, including lung mucosal tolerance. Lung DCs consist of functionally distinct subpopulations. We recently identified a lung IFNAR1+TNFR2+ conventional DC2 (iR2D2) population that promotes regulatory T cells in the lung. The lung R2D2 cells have tonic TNFR2 and IFNAR1 signaling at the steady-state. R2D2 depends on the tonic TNFR2 signals for survival and the tonic IFNAR1 signal to induce regulatory T cells in the lung. Last, the iR2D2 population is plastic promoting pathogenic Th2 responses during house dust mite-induced asthma in mice. These discoveries could lead to new therapies for asthma and COPD by restoring lung tolerance in these patients. Please see our related publications for details (Mansouri et al., 2020; Mansouri et al., 2019).

Promote lung mucosal vaccine responses by moDCs.
Lung infections, such as influenza and S. pneumococcal infection, are the 8th leading causes of death in U.S. Vaccines are the most effective and economical way to fight lung infections. Mucosal vaccines have the advantages of (i) neutralizing infection at the site of entry; (ii) limiting tissue damage; (iii) needle-free, ease of administration; (iv) suitability for mass vaccination during emergencies. Current vaccines in the clinic do not generate strong vaccine responses in lung mucosa. Cyclic dinucleotides (CDNs) are promising mucosal vaccine adjuvants. They elicit potent and balanced humoral and cellular immune response protecting animals from virus and bacterial infection. CDNs include cyclic di-AMP (CDA), cyclic di-GMP (CDG), and 2’5’-3’5’-cyclic 2 GMP-AMP (2’3’-cGAMP). STING (stimulator of interferon genes) is the mammalian receptor for CDNs. We first showed that the mucosal adjuvant CDNs enhance antigen uptake and process in animals and directly activates lung DCs in vivo. We further showed that STING-dependent TNFα production is critical for the mucosal adjuvant activity of CDNs in vivo. We recently found that the non-migratory moDCs promote CDNs vaccine adjuvant responses, including lung IgA and lung TFH responses in lung mucosa. Last, we showed that transmembrane TNF from TNFR2(-) cDC2 and TNFR2 expression on moDCs are essential for CDNs-induced vaccine responses in lung mucosa. With these mechanistic insights, we are excited to develop methods to enhance lung mucosal vaccine responses in non-mucosal vaccines. Please see our related publications for details (Blaauboer et al., 2014; Blaauboer et al., 2015; Mansouri et al., 2019)

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Understand the function of common human STING alleles.
STING, also known as MPYS, TMEM173, MITA, promotes type I IFN production in response to CDNs. STING/MPYS also inhibits cell growth and can mediate cell death. The human STING gene is highly heterogeneous and has population stratification. R71H-G230A R293Q (HAQ) is the 2nd most common human STING allele. Other common human STING alleles include G230A-R293Q (AQ), R23H (H232). All modern humans were from a single migration out of Africans 50k~70k years ago. Strikingly, AQ-STING was rapidly replaced by HAQ-STING in non-Africans suggesting a strong natural selection for HAQ over AQ in non-Africans, especially in East Asians. To understand the function of HAQ, we generated the HAQ knock-in mouse where three mutations: H71, A230, and Q293, were introduced into the endogenous mouse STING gene. We found that the HAQ mice were defective to generate type I IFN in response to CDNs. Furthermore, the Pneumovax®23 vaccines did not protect HAQ mice form pulmonary S. pneumococcal infection. The decreased ability of HAQ-STING to make type I IFNs were also observed in human HAQ individuals. Thus, it remains unclear why the HAQ-STING allele was selected in East Asians. Our ongoing research aims to answer this question and reveal an additional function for this popular and evolutional essential human HAQ-STING allele. Please see our related publications for details (Jin et al., 2013; Jin et al., 2011a; Jin et al., 2010; Jin et al., 2008; Jin et al., 2011b; Patel et al., 2017a, b; Patel and Jin, 2018).

Professional Societies

  • American Association of Immunologists
  • International Cytokine and Interferon Society
  • Society of Mucosal Immunology

Honors & Awards

  • 2012 – Marie Curie Fellow – European Commission
  • 2015 – The Gary and Janis Grover Young Scientist Award- Albany Medical College

Patents

  • Targeting lung-resident TNFR2+ cDC2 (R2D2) subpopulation to treat asthma [US 62/805.074] (UF17365)
  • Targeting moDC’s to enhance vaccine efficacy on the mucosal surface [US 62/737.154] (UF17355)

Grant Support

  • Ongoing Research Support
    • NIH-5R01AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – 2014 ~2020NIH-R21AI132865: Mechanisms of STING-dependent IFNgamma production during pulmonary pneumococcal infection – 2018~2020
  • Completed Research Support
    • NIH-R21AI125999: Impact of Human STING Variants on Pneumococcal Vaccine Effectiveness – 2016~2018
    • NIH-R56AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – July 2014 ~ Nov 2014.
    • NIH-R21AI099346 (Subcontract): Mouse Modeling of a Human STING Gene Variant for Infectious Disease – 2012 ~ 2015.

Publications

  • Blaauboer, S.M., Gabrielle, V.D., and Jin, L. (2014). MPYS/STING-mediated TNF-alpha, not type I IFN, is essential for the mucosal adjuvant activity of (3′-5′)-cyclic-di-guanosine-monophosphate in vivo. J Immunol 192, 492-502.
  • Blaauboer, S.M., Mansouri, S., Tucker, H.R., Wang, H.L., Gabrielle, V.D., and Jin, L. (2015). The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife 4.
  • Mansouri, S., Katikaneni, D.S., Gogoi, H., Pipkin, M., Machuca, T.N., Emtiazjoo, A.M., and Jin, L. (2020). Lung IFNAR1hi TNFR2+ cDC2 promotes lung regulatory T cells induction and maintains lung mucosal tolerance at steady-state. Mucosal Immunol In Press.
  • Mansouri, S., Patel, S., Katikaneni, D.S., Blaauboer, S.M., Wang, W., Schattgen, S., Fitzgerald, K., and Jin, L. (2019). Immature lung TNFR2(-) conventional DC 2 subpopulation activates moDCs to promote cyclic di-GMP mucosal adjuvant responses in vivo. Mucosal Immunol 12, 277-289.
  • Patel, S., Blaauboer, S.M., Tucker, H.R., Mansouri, S., Ruiz-Moreno, J.S., Hamann, L., Schumann, R.R., Opitz, B., and Jin, L. (2017a). The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele. J Immunol 198, 776-787.
  • Patel, S., Blaauboer, S.M., Tucker, H.R., Mansouri, S., Ruiz-Moreno, J.S., Hamann, L., Schumann, R.R., Opitz, B., and Jin, L. (2017b). Response to Comment on “The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele”. J Immunol 198, 4185-4188.
  • Patel, S., and Jin, L. (2018). TMEM173 variants and potential importance to human biology and disease. Genes Immun. 20(1): 82-89
  • Jin, L., Getahun, A., Knowles, H.M., Mogan, J., Akerlund, L.J., Packard, T.A., Perraud, A.L., and Cambier, J.C. (2013). STING/MPYS mediates host defense against Listeria monocytogenes infection by regulating Ly6C(hi) monocyte migration. J Immunol 190, 2835-2843.
  • Jin, L., Hill, K.K., Filak, H., Mogan, J., Knowles, H., Zhang, B., Perraud, A.L., Cambier, J.C., and Lenz, L.L. (2011a). MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol 187, 2595-2601.
  • Jin, L., Lenz, L.L., and Cambier, J.C. (2010). Cellular reactive oxygen species inhibit MPYS induction of IFNbeta. PLoS One 5, e15142.
  • Jin, L., Waterman, P.M., Jonscher, K.R., Short, C.M., Reisdorph, N.A., and Cambier, J.C. (2008). MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol 28, 5014-5026.
  • Jin, L., Xu, L.G., Yang, I.V., Davidson, E.J., Schwartz, D.A., Wurfel, M.M., and Cambier, J.C. (2011b). Identification and characterization of a loss-of-function human MPYS variant. Genes Immun 12, 263-269.
  • Please visit Pubmed for a complete list of publications: https://www.ncbi.nlm.nih.gov/myncbi/lei.jin.1/bibliography/public/