Dennis Lindell, PhD

Dennis Lindell, PhD


Children's Title: Principal Investigator, Seattle Children's Research Institute

Academic Title: Assistant Professor, Department of Pediatrics, University of Washington

Research Center: Center for Immunity and Immunotherapies

"The lost innocence that comes with childhood disease can either be simply sorrowful or it can feed us with the energy and creativity to advance medicine. I come to work each day for those children unlucky enough to be born premature in the peak of RSV season — for the children with asthma who cannot breathe but do not even understand why. I work so that we may help kids who struggle to breathe: so that they, too, can run the way only children run — not for exercise or competition, but just because it feels good and makes them feel alive."

    • Schaller MA, Logue H, Mukherjee S, Lindell DM, Coelho AL, Lincoln P, Carson WF 4th, Ito T, Cavassani KA, Chensue SW, Hogaboam CM, Lukacs NW, Kunkel SL
      Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1.
      20808960 PloS one , 2010 Aug. 17 : e12172
    • Lukacs NW, Smit JJ, Mukherjee S, Morris SB, Nunez G, Lindell DM
      Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation.
      20624950 Journal of immunology (Baltimore, Md. : 1950) , 2010 Aug. 15 : 2231-9
    • Cavassani KA, Carson WF 4th, Moreira AP, Wen H, Schaller MA, Ishii M, Lindell DM, Dou Y, Lukacs NW, Keshamouni VG, Hogaboam CM, Kunkel SL
      The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth.
      20130237 Blood , 2010 June 3 : 4403-11
    • Kallal LE, Schaller MA, Lindell DM, Lira SA, Lukacs NW
      CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC.
      20101616 European journal of immunology , 2010 Apr, : 1042-52
    • Lindell DM, Berlin AA, Schaller MA, Lukacs NW
      B cell antigen presentation promotes Th2 responses and immunopathology during chronic allergic lung disease.
      18769622 PloS one , 2008 Sept. 3 : e3129
    • Lindell DM, Lane TE, Lukacs NW
      CXCL10/CXCR3-mediated responses promote immunity to respiratory syncytial virus infection by augmenting dendritic cell and CD8(+) T cell efficacy.
      18624292 European journal of immunology , 2008 Aug. : 2168-79
    • Lukacs NW, Smit JJ, Schaller MA, Lindell DM
      Regulation of immunity to respiratory syncytial virus by dendritic cells, toll-like receptors, and notch.
      18419253 Viral immunology , 2008 June : 115-22
    • Smit JJ, Lindell DM, Boon L, Kool M, Lambrecht BN, Lukacs NW
      The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections.
      18320041 PloS one , 2008 Mar. 5 : e1720
    • Gordon SB, Kayhty H, Molyneux ME, Haikala R, Nurkka A, Musaya J, Zijlstra EE, Lindell D, French N
      Pneumococcal conjugate vaccine is immunogenic in lung fluid of HIV-infected and immunocompetent adults.
      17544493 The Journal of allergy and clinical immunology , 2007 July : 208-10
    • Lukacs NW, Smit J, Lindell D, Schaller M
      Respiratory syncytial virus-induced pulmonary disease and exacerbation of allergic asthma.
      17684333 Contributions to microbiology , 2007 : 68-82
    • Lindell DM, Ballinger MN, McDonald RA, Toews GB, Huffnagle GB
      Diversity of the T-cell response to pulmonary Cryptococcus neoformans infection.
      16861640 Infection and immunity , 2006 Aug. : 4538-48
    • Lindell DM, Moore TA, McDonald RA, Toews GB, Huffnagle GB
      Distinct compartmentalization of CD4+ T-cell effector function versus proliferative capacity during pulmonary cryptococcosis.
      16507900 The American journal of pathology , 2006 Mar. : 847-55
    • Lindell DM, Moore TA, McDonald RA, Toews GB, Huffnagle GB
      Generation of antifungal effector CD8+ T cells in the absence of CD4+ T cells during Cryptococcus neoformans infection.
      15944298 Journal of immunology (Baltimore, Md. : 1950) , 2005 June 15 : 7920-8


Medical/Professional School

University of Michigan, Ann Arbor, Immunology


Pulmonary Disease, University of Michigan, Ann Arbor
Pathology - Clinical, University of Michigan, Ann Arbor

Research Description

My laboratory is broadly interested in the mechanisms that control immunogenicity versus tolerance in the lungs. While exchanging the air we breathe, the lungs are continuously sampling the environment for the presence of disease causing pathogens. Health, (and in many cases, survival) depends upon simultaneously responding appropriately to dangerous pathogens, while tolerating the vast majority of harmless potential stimuli. Cells resident in the lungs are an important first line of communication for the immune system, and their behavior in response to pathogenic or other environmental stimuli influences the quality and magnitude of disease and disease resolution. These functions include, among others: microbicidal activity, the production of mediators to recruit and activate inflammatory cells (cytokines and chemokines), and redistribution to other tissues (lymph nodes) for interactions with T lymphocytes.

Within the greater field of pulmonary immunology, we have chosen to focus on a number of factors:

1) Biology of antigen-presenting cells in the lungs (especially dendritic cells and B lymphocytes), and how it influences pulmonary disease. One primary project involves the role of B cells as antigen-presenting cells during asthma and viral exacerbation of asthma. B cells are unique in that they are the only antigen presenting cell capable of antigen-specificity. Our studies have found that antigen-specific B cells accumulate in the lungs throughout chronic allergic disease, and have the ability to elicit Th2 cytokines from CD4+ T cells. These Th2 cytokines, including IL-4, IL-5, and IL-13 are central to the pathogenesis of asthma. We are ultimately interested in whether it may be possible to 1) pharmacologically target B cell antigen-presentation in asthma, or 2) manipulate a patient?s own (autologous) B cells to render them tolerogenic, rather than disease promoting, and infuse them back into the patient as a cellular therapy.

2) Regulatory T cell (Treg) trafficking and function in the lungs. Tregs are a subset of T lymphocytes that are critical for controlling inappropriate immune responses. Our studies examine the activation, trafficking, and function of these cells in a variety of pulmonary disease settings. Chemokines are small mediators produced during inflammation. The types of chemokines produced help dictate what types of inflammatory cells are attracted to the inflamed tissue. Our studies, as well as those by others, have thus far have identified two chemokine receptors, CXCR3 and CCR4, that appear to be important for the trafficking of regulatory T cells to the lungs following Th1 and Th2 mediated inflammation, respectively. However, there is considerable redundancy in chemokine receptor/ligand systems, with one cell type expressing many receptors, and multiple ligands for each receptor. Our studies seek to understand the temporal-spatial relationship during lung disease between inflammatory cells/mediators and inflammation-resolving Tregs, with the ultimate goal of modulating inflammation through Tregs.

We utilize a combination of in vivo and in vitro approaches to gain insight into these processes, including animal models of asthma, as well as viral infection.

Research Focus Area

Infectious Disease, Host: Pathogen Interaction, Pulmonary, Allergy, Immunology