Physician Investigator (Cl) Allergy and Clinical Immunology Unit, Mass General Research Institute

Assistant Professor of Medicine Harvard Medical School

Assistant Physician Allergy and Clinical Immunology Unit, Massachusetts General Hospital

M.D.; Ph.D. Yale University School of Medicine 2009

allergens; antigen-presenting cells; basophils; chemokines; drug allergies; hypersensitivity; innate immunity; papain; th2 cells

The innate immune system plays a central role in adaptive immune initiation by sensing microbial invasion and environmental stress and using that information to promote specific adaptive immune outcomes. But how does the innate immune system do this?

In the case of Type-1 immunity, generally regarded as the responses against bacteria and viruses, dendritic cells in the periphery are activated through their pattern recognition receptors by microbial pathogen associated molecular patterns.

This leads to dendritic cell maturation, which is characterized by increased antigen presentation, upregulation of costimulatory molecules, migration to the draining lymph node, and secretion of cytokines involved in T helper cell skewing.

Thus, for Type-1 immunity the dendritic cell is capable of analyzing innate immune input to promote specific adaptive immune output.

Despite the fact that allergic diseases are the 6th leading cause of chronic disease, little is known about how they are initiated. There is evidence that the same pathways utilized in Type-1 immunity may not be involved in the initiation of Type-2, or allergic, immunity.

Dendritic cells have been shown to be essential for Th2-differentiation and Type-2 immune responses, but how they are activated, how they promote adaptive immune skewing, and whether additional cell types are required for the initiation of Type-2 immunity is unknown. Using the tools of cellular immunology, the Sokol lab seeks to elucidate the mechanisms behind the innate immune control of allergic disease.