Igyártó Research

Botond Igyarto, PhD

Contact

Name: Botond Igyártó, PhD
Position: Assistant Professor

233 South 10th Street
620 BLSB
Philadelphia, PA 19107

Telephone: 215-955-9698

The research in the Igyártó laboratory is centered around understanding dendritic cell (DC) biology and developing effective DC vaccines for infectious diseases, autoimmune diseases, allergy, and cancer. Many innovative projects are going on in the lab, only a few of which are highlighted below. Please reach out to us if you are hungry for more.

Research Projects

Intracellular monitoring by dendritic cells

LCs stay informed by sampling the intracellular content of the surrounding cells LCs stay informed by sampling the intracellular content of the surrounding cells through nanotubes/dendrites.

We recently identified that keratinocytes share gene expression fingerprint with the local DCs (LC) via mRNA transfer that likely involves nanotubes/dendrites. This communication form also allows DCs to monitor the intracellular niche of the surrounding non-hematopoietic cells and collect real-time information on possible infections and metabolic changes. We are working on firming up our findings and then planning to move on to systematically test the role of this communication form in promoting self-tolerance, cross-presentation, maintaining the epithelial barrier, intercellular communications, etc.

Determine how different DC subsets regulate humoral immune responses

DCs are professional antigen-presenting cells (APCs) that regulate all aspects of the adaptive immune response. However, our knowledge is very limited to how DC subsets regulate humoral immune responses (antibody responses). Since many vaccines’ effectiveness relies on the induction of neutralizing antibody (humoral) responses, understanding the mechanism by which DC subsets regulate humoral immune responses is crucial for the development of more effective vaccines. In this project, we aim to determine the mechanistic aspects of DC-regulated humoral immune responses.

Sequential Activation Model Sequential activation model. Based on this model the Langerhans cells (LCs) first initiate the differentiation of Tfh cells and then licensed by the Tfh cells migrate into the B cell area to deliver the intact antigen for B cell activation. The B cells then interact with the Tfh cells to promote their final maturation and in turn the B cells will differentiate into plasma cells and memory cells. The responses induced by LCs could be inhibited by high antigen dose and IL-10. We also discovered that cDC1s can prevent LCs from inducing humoral immune responses. The cDC1s were not able to drive significant humoral immune responses in steady state, but inflammatory signals enabled them.

How the absence of immune cells affects tissue homeostasis?

The effect of tissue environment on immune cells has been widely studied. It is well-documented that keratinocytes can regulate the immune response by affecting epidermal-resident, antigen-presenting Langerhans cell biology through secretion of cytokines and other factors. However, it is unknown whether the long-term absence of immune cells could affect the tissue homeostasis. We found that the long-term lack of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken into consideration at data interpretation.

One-step artificial APC for cancer immunotherapy and not just

The production and wide use of artificial antigen-presenting cells (aAPCs) in the clinic as cancer immunotherapeutics are hindered by the need for identifying immunogenic cancer antigens and production of recombinant patient-specific major histocompatibility complexes (MHC) loaded with these peptides. To overcome these limitations, we tested the idea of whether peptide-MHCs can directly be captured from cell lysates, including cancer cells using affinity beads, and used to initiate T cell responses. In theory, these affinity beads covered with the unknown peptide-MHC repertoire captured from the cancer cells could interact with a wide range of antigen-specific T cells and promote anti-cancer responses. Indeed, we found that we can successfully pull-down peptide-MHCs from cell lysates and the aAPCs generated using this technique were able to induce antigen-specific cytotoxic effector T cell responses that led to in vitro and in vivo tumor cell killing. In summary, we present here a novel technique to generate patient-specific aAPCs, that might have the potential to revolutionize the field of cancer vaccines and provide patients with a vaccine in matters of days at minimal costs.

One step aAPC Generation. Graphical representation of one-step aAPC generation. Tumor cell lysates are incubated with affinity beads that capture the peptide-MHC-I repertoire of the cancer cells. The beads are then used to activate cancer antigen-specific T cell clones that will ultimately kill the tumor cells.

Determine the immune mechanism of mRNA vaccines

mRNA vaccines formulated with lipid nanoparticles have been shown to a induce robust and long-lasting humoral immune response that protect from subsequent infections. Their immune mechanism is largely unknown, thus in collaboration with Drs. Norbert Pardi and Drew Weissman at UPenn, we are on a quest to determine the immune mechanism of the mRNA vaccines.

 Highly motivated post-docs interested in joining the lab should contact the PI directly.