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R. Lee Reinhardt, Ph.D.


  • Assistant Professor, Department of Biomedical Research, National Jewish Health
  • Assistant Professor, Department of Immunology & Microbiology, University of Colorado SOM

1400 Jackson St, K817
Denver, CO 80206
Phone: 303-270-2717
Email: ReinhardtL@NJHealth.org
​The long-term goal of our research is to expand our understanding of the following: 1) The cellular and molecular events that influence allergic disease susceptibility and initiation; 2) The mechanisms regulating immunity to parasites; 3) The role and relationship between follicular T helper (Tfh), T-helper 2 (Th2), and follicular regulatory (Tfr) cells in the development/suppression of allergic disease and germinal center-derived lymphomas, and 4) The mechanisms driving interferon-mediated autoinflammatory diseases. 

Our work has largely focused on understanding the generation, function, and cell fate decisions of CD4+ T-helper (Th) cell subsets in vivo following infection with various pathogens. To do this, we make use of various cytokine and transcription factor reporter mouse models to elucidate Th1, Th2, Tfh, and Tfr development and function. These models provide the opportunity to visualize immune cell function directly in vivo using flow cytometery in combination with conventional immunofluorescence (Figure 1) and live tissue imaging using multi-photon microscopy (Figure 2).



In addition, we have continued to develop second-generation cytokine and transcription factor reporter systems to address unanswered questions in allergic inflammation, CD4 T cell biology, and cytokine regulation (Figure 3).



Together, these studies have provided the basis to understand an unexpected, yet important bifurcation in type-2 immunity orchestrated by follicular T cells in the lymphoid tissues and Th2 cells in mucosal non-lymphoid tissues (Figure 4).



Beyond visualizing cellular function, these reporter animals provide excellent tools to study gene expression, gene function, and epigenetic gene regulation in physiologic settings. Specifically, these reporter systems allow us to isolate rare populations of innate and adaptive immune cells from various tissues to explore their transcriptional programs and epigenetic profiles at various times during an immune response. We have now established collaborations to continue to investigate these cellular programs and epigenetic events at the single cell level.

We have recently expanded our focus to explore three new areas.

First, we are interested in understanding the relationship between Tfh cells and Tfr cells in chronic parasitic infections and during the development and progression of B cell lymphomas (Fig. 5). 


Second, we have expanded our research in IFN-gamma driven autoinflammatory diseases (Figure 6) to look at rare childhood syndromes. We have generated a new mouse model harboring a human mutation present in rare proteasome-associated autoinflammatory syndromes (PRAAS). This is the first PRAAS-specific mouse model, and this pre-clinical model will allow us to better understand how type-1 and type-2 interferons are involved in disease pathogenesis. We believe mutations in subunits of the immunoproteasome create a pathogenic feedback loop where chronic production of IFNs promote increased inflammation and pathology.


Third, we are exploring various mechanisms related to how early-life helminth exposure can prevent or ameliorate allergic disease symptoms (Figure 6). The goal is to uncover novel mechanisms that can be leveraged into therapies that mimic the beneficial effects of helminths on allergic disease susceptibility


































​Current Lab Members

Postdocs and Fellows:

Preeyam S Patel, PhD
​​
I received my Ph.D. at the University of Alabama at Birmingham in the laboratory of John Kearney. My dissertation focused on modifications to the early life B cell repertoire as the result of microbial exposure and its effects on the development of allergies and asthma. In the Reinhardt laboratory I am interested in further investigating how early life events can alter development of the microbiota and T cell subsets. My current project focuses on the role of AP-1 transcription factors in ILC2 subset function and generation.
  Graduate Students:

Mark Dell'Aringa

My thesis research is focused on investigating the role of Notch signaling in Follicular T helper (Tfh) cells and T helper 2 (Th2) cells in the context of type 2 immunity. Briefly, I use intestinal helminth infections to induce a strong type 2 immune response in mice and study the phenotype of Tfh and Th2 cells in various genetically modified mouse strains.​
 Research Scientists:

Ivy K Brown, MSc (Lab Manager)

I obtained my master’s degree in Molecular Biology at the University of Brussels in Belgium, where I specialized in human health.  My current research projects focus on characterizing mouse models of various interferonapathies relevant to human disease.  We aim to investigate the cellular mechanisms behind these disorders with an ultimate goal of developing therapies for treatment.  I am also ​responsible for general lab management.
 
Past Lab Members: (current position)
Postdocs and Fellows:
Thomas O’Brien (Beckman-Coulter)

Graduate Students:
Katherine Bao (Postdoc Genentech)

Research Scientists/ Lab Managers:
Ann Miller (Duke University)
Julio Barrera (Duke University)

Undergraduate Students:
Jingxiao Jin (Baylor Medical School)
Simon Jiang (Duke University; Element Genomics)

Early Career Scientists/ Pre-collegiate Students:
Rebecca Shen (Stanford)

Reinhardt Lab (Winter 2017)
Mark, Preeyam, and Ivy - Welcome to Denver!


Reinhardt Lab (Winter 2014)
Tommy, Mark, Katherine, Jingxiao and Ann (not pictured) – 
The Fantastic First Five



Journal Articles: (* denotes equal contribution)
  1. Bao K, Carr T, Wu J, Barclay W, Jin J, Ciofani M, Reinhardt RL (2016) BATF modulates the Th2 locus control region and regulates CD4+ T cell fate during anti-helminth immunity. J Immunol 197 (11):4371-4381
  2. O’Brien TF, Bao K, Ang W.X.G, Abraham S, Reinhardt RL (2016) L-4 and IL-13 expression by Natural Killer T cells is tightly regulated throughout development and in settings of allergic inflammation. Mucosal Immunology 9(3):597-609
  3. Reinhardt RL, Liang HE, Bao K, Price AE, Mohrs M, Kelly BL, Locksley RM (2015) A novel model for IFN-gamma-mediated autoinflammatory syndromes. J Immunol 194(5):2358-68
  4. Publicover J, Gaggar A, Nishimura S, Van Horn CM, Goodsell A, Muench MO, Reinhardt RL, van Rooijen N, Wakil AE, Peters M et al: (2013) Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B. The Journal of clinical investigation 123(9):3728-3739.
  5. Price AE, Reinhardt RL, Liang HE, Locksley RM (2012): Marking and Quantifying IL-17A-Producing Cells In Vivo. PLoS One, 7(6):e39750. 
  6. Liang HE*, Reinhardt RL*, Bando JK, Sullivan, BM, Locksley RM (2011) Divergent expression of IL-4 and IL-13 define unique functions in type 2 immunity. Nature immunology.13(1):58-66. (*equal contribution) 
  7. Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM (2010) Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci USA.107(25):11489-94. 
  8. Reinhardt RL, Liang HE, Locksley RM (2009) Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 10(4): 385-393.
  9. Reinhardt RL*, Hong S*, Kang SJ, Wang ZE, Locksley RM (2006) Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1 differentiation. J Immunol 177(3): 1618-1627. (*equal contribution)
  10. Scheu S, Stetson DB, Reinhardt RL, Leber JH, Mohrs M, and Locksley RM (2006) Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 7(6): 644-651.
  11. Park HS, Costalonga M, Reinhardt RL, Dombek PE, Jenkins MK, Cleary PP (2004) Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection. Eur J Immunol 34(10): 2843-2853.
  12. Stetson DB, Mohrs M, Reinhardt RL, Baron JL, Wang ZE, Gapin L, Kronenberg M, Locksley RM (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198(7): 1069-1076.
  13. Reinhardt RL, Bullard DC, Weaver CT, Jenkins MK (2003) Preferential accumulation of antigen-specific effector CD4 T cells at an antigen injection site involves CD62E-dependent migration but not local proliferation. J Exp Med 197(6): 751-762.
  14. Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E, Rudensky AY, Jenkins MK (2003) Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19(1): 47-57.
  15. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, L envik T, Lund T, Blackstad M, Du JB, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893): 41-49.
  16. McSorley SJ, Asch S, Costalonga M, Reinhardt RL, Jenkins MK (2002) Tracking salmonella-specific CD4 T cells in vivo reveals a local mucosal response to a disseminated infection. Immunity 16(3): 365-377.
  17. Reinhardt RL, Khoruts A, Merica R, Zell T, Jenkins MK (2001) Visualizing the generation of memory CD4 T cells in the whole body. Nature 410(6824): 101-105. 
  18. Reichert P, Reinhardt RL, Ingulli E, Jenkins MK (2001) Cutting edge: in vivo identification of TCR redistribution and polarized IL-2 production by naive CD4 T cells. J Immunol 166(7): 4278-4281.
  19. Erickson HA, Reinhardt RL, Hermanson JB, Panoskaltsis-Mortari A, Pennell CA (2001) Visualization of immunotoxin-mediated tumor cell death in vivo. Clin Cancer Res 7(3 Suppl): 890s-894s.
  20. Merica R, Khoruts A, Pape KA, Reinhardt RL, Jenkins MK (2000) Antigen-experienced CD4 T cells display a reduced capacity for clonal expansion in vivo that is imposed by factors present in the immune host. J Immunol 164(9): 4551-4557.
  21. Martin EL, Reinhardt RL, Baum LL, Becker MR, Shaffer JJ et al. (2000) The effects of ultraviolet radiation on the moderate halophile Halomonas elongata and the extreme halophile Halobacterium salinarum. Can J Microbiol 46(2): 180-187.

Reviews:
  1. Bao K, Reinhardt RL (2015) The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine 75(1):25-37
  2. Reinhardt RL, Kang SJ, Liang HE, Locksley RM (2006) T helper cell effector fates--who, how and where? Curr Opin Immunol 18(3): 271-277.
  3. Stetson DB, Voehringer D, Grogan JL, Xu M, Reinhardt RL, Scheu S, Kelly BL, Locksley RM (2004) Th2 cells: orchestrating barrier immunity. Adv Immunol 83: 163-189.
  4. Reinhardt RL, Jenkins MK (2003) Whole-body analysis of T cell responses. Curr Opin Immunol 15(4): 366-371.
  5. Jenkins MK, Khoruts A, Ingulli E, Mueller DL, McSorley SJ, Reinhardt RL, Itano A, Pape KA (2001) In vivo activation of antigen-specific CD4 T cells. Annu Rev Immunol 19: 23-45.