Lei Jin, PhD, MSc

Lei Jin, PhD, MSc
Associate Professor of Medicine

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




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

Research Interests

Dr. Jin’s lab researches (a) lung tolerance and inflammation; (b) common human MPYS (a.k.a STING) variants HAQ and AQ. We use mouse models to dissect the in vivo mechanisms. We use primary human samples to establish human relevance. We are committed to translational research that improves human health and medicine.

  • The tolerogenic lung epithelial cells IFNβ – TNFR2+ cDC2 – Tregs axis – The lung is a tolerogenic organ. Loss of lung mucosal tolerance causes chronic inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 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. Our goal is to understand the underlying mechanism of lung tolerance and design new therapy that restore lung tolerance in chronic lung disease patients and achieve a cure.

Lung DCs sense environmental cues and direct lung immune responses. We recently proposed a lung epithelial IFNβ – TNFR2+ cDC2 (R2D2) – Tregs axis that maintains lung tolerance at a steady state. The lung R2D2 cells depend on the tonic TNFR2-RelB signals for survival and the tonic IFNβ-IFNAR1-ERK2 signal to induce lung regulatory T cells. Interestingly, the R2D2 population is plastic promoting pathogenic immune responses during house dust mite-induced asthma. Importantly, intranasal administration of IFNβ reprograms pathogenic R2D2 back to tolerogenic R2D2 and restores lung tolerance in asthmatic mice. Please see our related publications for details (Mansouri et al., 2021 Science Immunology; Mansouri et al., 2020 Mucosal Immunology; Mansouri et al., 2019, Mucosal Immunology).

  • Lung moDCs in lung tissue-resident immune response.
    moDCs are differentiated from recruiting inflammatory monocyte. Similar to cDCs, moDCs prime diverse T cell responses suggesting that moDCs might be a heterogeneous population. Different from cDCs, lung moDCs do not migrate to the draining lymph nodes. While investigating the mucosal adjuvant activity of CDNs, we identified crosstalk between lung cDC2 and moDCs. We found that CDNs directly activate lung R2D2, which activates the non-migratory moDCs via TNF that promotes IgA and TFH responses in lung mucosa. Later, we showed that a subpopulation of moDCs can differentiate into Bcl6+ moDCs in the lung to promote the generation of lung TRM. The understanding of lung-tissure resident immune response will help generate better vaccines to fight respiratory infections. Please see our related publications for details (Mansouri et al., 2019, Mucosal Immunology,  Mansouri, et al., 2021, Journal of Immunology)
  • Common human MPYS variants HAQ and AQ.
    MPYS, also known as STING, TMEM173, senses cyclic dinucleotides (CDNs) and induces type I IFNs and TNF. MPYS plays a critical role in infection, inflammation, and cancer immunotherapy. We first discovered that the human MPYS gene is highly heterogeneous and shows population stratification. The R71H-G230A-R293Q (HAQ) is the 2nd most common human MPYS allele carried by ~63% of East Asians. G230A-R293Q (AQ) is carried by ~40% of Africans. All modern humans were from a single migration out of Africans 50k~70k years ago. Strikingly, AQ was replaced by HAQ in non-Africans suggesting a strong natural selection for HAQ over AQ in non-Africans. To understand the underlying mechanism for this natural selection, we generated HAQ and AQ knock-in mice. We found that adult AQ mice have less fat weight than the HAQ or WT mice, which might be disadvantageous during the out-of-Africa migration. We propose that MPYS has a previously unknown function in fatty acid metabolism that is altered by the AQ allele. Understanding the natural selection of HAQ over AQ will reveal the fundamental function of MPYS in human health. Please see our related publications for details ( Patel et al., 2017, Journal of Immunology; Sebastian M et al., 2020, JCI Insight, and Mansouri S,  et al., 2022, Journal of Immunology).

Teaching Interests

  1. Principals of Immunology GMS6140 – Lecturer [9 lectures]
  2. Mucosal Immunology GMS5905 – Director

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


  • 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-R01HL152163: Lung IDO-1+ TNFR2+ cDC2 subset in control of lung mucosal tolerance: Mechanism and Application– 2021 ~2024
  • Completed Research Support
    • NIH-5R01AI110606: Mechanisms of STING-Mediated Mucosal Vaccine Adjuvant Activity of Cyclic di-GMP – 2014 ~2020
    • NIH-R21AI132865: Mechanisms of STING-dependent IFNgamma production during pulmonary pneumococcal infection – 2018~2020
    • 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.


  • Mansouri, S, Katikaneni, D, Gogoi, H, Singh, A, Aybar, A, de Lartigue, G., and Jin, L. MPYS Modulate Fatty Acid Metabolism and Immune Tolerance at Homoeostasis Independent of Type I IFNs J Immunol, (2022). May 15th, Highlighted in this Issue, top 10% of the articles published in the Journal.
  • Mansouri, S., Gogoi, H, Mauricio Pipkin, Tiago N Machuca, Amir M. Emtiazjoo, Sharma, A. K., and Jin, L. In vivo reprogramming pathogenic lung TNFR2+ cDC2 by IFNβ inhibits HDM-induced asthma. Sci Immunol. 2021 Jul 9;6(61). [The identification of the tolerogenic IFNβ-IFNAR1-ERK2 pathway in R2D2 cells]
  • Mansouri, S, Katikaneni, DGogoi, H, and Jin, L. moDCs differentiates into Bcl6+ mature moDCs to promote cyclic di-GMP vaccine adjuvant-induced memory TH cells in the lung. J Immunol, (2021). May 1, 206 (9) 2233-2245. [The identification of lung Bcl6+ moDCs promoting lung TRM]
  • Sebastian M, Hsiao CJ, Futch HS, Eisinger RS, Dumeny L, Patel S, Gobena M, Katikaneni DS, Cohen J, Carpenter AM, Spiryda L, Heldermon CD, Jin L, Brantly ML. Obesity and STING1 genotype associate with 23-valent pneumococcal vaccination efficacy. JCI Insight. 2020 May 7; 5(9). [The first clinical trial on HAQ-MPYS]
  • 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 Immunol2020, 13, 595–608. [The identification of lung epithelial IFNβ- TNFR2+cDC2 –Tregs tolerogenic axis]
  • 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. Recommended in Faculty Opinions
  • Patel, S., and Jin, L. (2018). TMEM173 variants and potential importance to human biology and disease. Genes Immun. 20(1): 82-89 Readers’ Choice: The Best of Genes and Immunity 2019
  • Patel, S., Blaauboer, S.M., Tucker, H.R., Mansouri, S., Ruiz-Moreno, J.S., Hamann, L., Schumann, R.R., Opitz, B., and Jin, L. (2017). The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele. J Immunol 198, 776-787. Highlighted in this Issue, top 10% of the articles published in the Journal.
  • 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.
  • 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.
  • Jin, L., Hill, K.K., Filak, H., Mogan, J., Knowles, H., Zhang, B., Perraud, A.L., Cambier, J.C., and Lenz, L.L. (2011). 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., 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.
  • 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. [The original paper on MPYS/STING]

A complete list of publications: