Lukacs Laboratory

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Dendritic Cell Biology

Over the years our research has explored several evolving responses related to initiation and maintenance of immune responses.  Early data indicated that leukocyte interaction with adhesion molecules at sites of inflammation amplify responses by activation of chemokines through integrin-mediated inflammatory responses.  Subsequently, as we explored how innate immune mediators such as TLRs were involved in the activation of responses our studies outlined that TLR3 and TLR7/MyD88 play intricate roles in driving a productive immune response to viral infection.  When absent, the immune response that developed became more pathogenic and linked to the innate immune response, especially DC. As we continued to explore mechanisms of APC function that were driven by TLR-mediated activation we found that Notch ligand expression on DC could regulate and promote specific immune responses, including Th17, in a permissive environment.  We continue to explore novel mechanisms of DC activation, such as Autophagy and Sirt1 activation that regulate acquired immune responses to better understand how APC activation can modulate the initiation and maintenance of a pathogenic immune response.  More recently, we have examined the cellular metabolism in controlling DC function to determine how metabolism regulates innate immune responses. We’ve also been able to demonstrate that an early-life RSV infection leads to long-term changes in myeloid cell populations in animals that reflect the exacerbation response during later asthmatic disease. These data will also be fundamental for proper vaccine development, especially for pathogenic targets that have been difficult to design a proper strategy, such as with RSV vaccines.

 

Publications

  1. Malinczak CA, Fonseca W, Mire MM, Parolia A, Chinnaiyan A, Rasky AJ, Morris S, Yagi K, Bermick JR, Lukacs NW. Sex-associated Early-life viral Innate Immune Response is Transcriptionally Associated with chromatin remodeling of Type-I IFN-inducible Genes. Mucosal immunology 2023.
  2. Narayanan S, Elesela S, Rasky AJ, Morris SH, Kumar S, Lombard D, Lukacs NW. ER stress protein PERK promotes inappropriate innate immune responses and pathogenesis during RSV infection. Journal of leukocyte biology 2022; 111: 379-389.
  3. Malinczak CA, Parolia A, Fonseca W, Morris S, Rasky AJ, Bawa P, Zhang Y, Mire MM, Ziegler SF, Ptaschinski C, Chinnaiyan AM, Lukacs NW. TSLP-Driven Chromatin Remodeling and Trained Systemic Immunity after Neonatal Respiratory Viral Infection. Journal of immunology 2021; 206: 1315-1328.
  4. Elesela S, Morris SB, Narayanan S, Kumar S, Lombard DB, Lukacs NW. Sirtuin 1 regulates mitochondrial function and immune homeostasis in respiratory syncytial virus infected dendritic cells. PLoS pathogens 2020; 16: e1008319.
  5. Malinczak CA, Fonseca W, Rasky AJ, Ptaschinski C, Morris S, Ziegler SF, Lukacs NW. Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease. Mucosal immunology 2019; 12: 969-979.
  6. Owczarczyk AB, Schaller MA, Reed M, Rasky AJ, Lombard DB, Lukacs NW. Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus-Induced Immune Responses. Journal of immunology 2015; 195: 1637-1646.
  7. Jang S, Smit J, Kallal LE, Lukacs NW. Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration. Journal of leukocyte biology 2013; 94: 5-15.
  8. Morris S, Swanson MS, Lieberman A, Reed M, Yue Z, Lindell DM, Lukacs NW. Autophagy-mediated dendritic cell activation is essential for innate cytokine production and APC function with respiratory syncytial virus responses. Journal of immunology 2011; 187: 3953-3961.
  9. Kallal LE, Schaller MA, Lindell DM, Lira SA, Lukacs NW. CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC. Eur J Immunol 2010; 40: 1042-1052.
  10. 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. PloS one 2008; 3: e1720.
  11. Rudd BD, Luker GD, Luker KE, Peebles RS, Lukacs NW. Type I interferon regulates respiratory virus infected dendritic cell maturation and cytokine production. Viral Immunol 2007; 20: 531-540.
  12. Smit JJ, Rudd BD, Lukacs NW. Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. The Journal of experimental medicine 2006; 203: 1153-1159.