Bao, K, Carr, T, Wu, J, Barclay, W, Jin, J, Ciofani, M, and Reinhardt, RL. "BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity." Journal of immunology (Baltimore, Md. : 1950) 197, no. 11 (December 2016): 4371-4381.
Richard Lee Reinhardt, PhD
My current research objectives are directed toward understanding immune responses in vivo. Much work has been invested in determining the molecular events that drive CD4+ T helper cell differentiation in vitro as well as the critical cellular players necessary for initiating an adaptive immune response within lymphoid tissues. However, it has been difficult to address true CD4+ T helper cell biology due to a lack of experimental systems designed to access CD4+ T cell function directly in vivo.
Thus, my specific interests are developing new methods to study CD4+ T cells during the effector and memory phase of the immune response in the context of different parasitic, bacterial, and viral models of infection. I am interested in comparing the phenotype and function of CD4+ T-helper cells residing in the secondary lymphoid tissues (such as spleen and lymph nodes) to those residing at sites of infection. In particular, my goal is to understand the relationship between cytokine-producing T follicular helper cells (Tfh) and conventional T-helper type 1 (Th1), T-helper type 2, and follicular regulatory T cells (Tfr). Particular attention will be focused on elucidating the role that these functionally distinct T-helper cells play in maintaining immunologic memory, and how dis-regulation of these subsets can impact B cell lymphoma development, asthma, and autoinflammatory disease. We are also committed to understanding how exposure to microbes in early-life can influence T-helper cell differentiation, regulatory function, and disease onset. Currently our models focus on understanding how helminth colonization impacts allergic disease onset and severity.
The broad, long term goals of this research program are to understand the cellular and molecular events driving the differentiation of naïve CD4+ T cells into different T-helper cell subsets, and to investigate the function, plasticity, and cell fate decisions of these cells during a primary and secondary immune response. Elucidating the signals and events that regulate T-helper cell differentiation (i.e. Th1, Th2,Tfh, Treg,Tfr) and function (i.e. cytokine production) will have broad implications in basic CD4+ T cell biology and provide important insights that will aid in the fight against infectious disease, cancer, allergic asthma, and autoinflammatory diseases.
Education and Training
- Graduate Research, Graduate School, University of Minnesota, Twin Cities, 1997 - 2002
- Ph.D., University of Minnesota, Twin Cities, 2002
O'Brien, TF, Bao, K, Dell'Aringa, M, Ang, WXG, Abraham, S, and Reinhardt, RL. "Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation." Mucosal immunology 9, no. 3 (May 2016): 597-609.
Bao, K, and Reinhardt, RL. "The differential expression of IL-4 and IL-13 and its impact on type-2 immunity." Cytokine 75, no. 1 (September 2015): 25-37. (Review)
Reinhardt, RL, Liang, H-E, Bao, K, Price, AE, Mohrs, M, Kelly, BL, and Locksley, RM. "A novel model for IFN-γ-mediated autoinflammatory syndromes." Journal of immunology (Baltimore, Md. : 1950) 194, no. 5 (March 2015): 2358-2368.
Publicover, J, Gaggar, A, Nishimura, S, Horn, CMV, Goodsell, A, Muench, MO, Reinhardt, RL, Rooijen, NV, Wakil, AE, Peters, M, Cyster, JG, Erle, DJ, Rosenthal, P, Cooper, S, and Baron, JL. "Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B." Journal of Clinical Investigation 123, no. 9 (2013): 3728-3739.
Price, AE, Reinhardt, RL, Liang, H-E, and Locksley, RM. "Marking and quantifying IL-17A-producing cells in vivo." PLoS ONE 7, no. 6 (2012).
Liang, H-E, Reinhardt, RL, Bando, JK, Sullivan, BM, Ho, I-C, and Locksley, RM. "Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. (Published online)" Nat Immunol 13, no. 1 (December 4, 2011): 58-66.
Price, AE, Liang, H-E, Sullivan, BM, Reinhardt, RL, Eisley, CJ, Erle, DJ, and Locksley, RM. "Systemically dispersed innate IL-13-expressing cells in type 2 immunity." Proc Natl Acad Sci U S A 107, no. 25 (June 22, 2010): 11489-11494.
Reinhardt, RL, Liang, H-E, and Locksley, RM. "Cytokine-secreting follicular T cells shape the antibody repertoire." Nat Immunol 10, no. 4 (April 2009): 385-393.
Reinhardt, RL, Hong, S, Kang, S-J, Wang, Z-E, and Locksley, RM. "Visualization of IL-12/23p40 in vivo reveals immunostimulatory dendritic cell migrants that promote Th1 differentiation." J Immunol 177, no. 3 (August 1, 2006): 1618-1627.
Scheu, S, Stetson, DB, Reinhardt, RL, Leber, JH, Mohrs, M, and Locksley, RM. "Activation of the integrated stress response during T helper cell differentiation." Nat Immunol 7, no. 6 (June 2006): 644-651.
Reinhardt, RL, Kang, S-J, Liang, H-E, and Locksley, RM. "T helper cell effector fates--who, how and where?." Curr Opin Immunol 18, no. 3 (June 2006): 271-277. (Review)
Park, H-S, Costalonga, M, Reinhardt, RL, Dombek, PE, Jenkins, MK, and Cleary, PP. "Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection." Eur J Immunol 34, no. 10 (October 2004): 2843-2853.
Stetson, DB, Voehringer, D, Grogan, JL, Xu, M, Reinhardt, RL, Scheu, S, Kelly, BL, and Locksley, RM. "Th2 cells: orchestrating barrier immunity." Adv Immunol 83 (2004): 163-189. (Review)
Stetson, DB, Mohrs, M, Reinhardt, RL, Baron, JL, Wang, Z-E, Gapin, L, Kronenberg, M, and Locksley, RM. "Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function." J Exp Med 198, no. 7 (October 6, 2003): 1069-1076.