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Research at Mass General
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Principal Investigator, Center for Immunology and Inflammatory Diseases
Assistant Physician, Massachusetts General Hospital
Instructor in Medicine, Harvard Medical School
Innate Immune Control of Allergy
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 6thleading 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.
Allergen control of dendritic cell activation and migration
Exposure to allergens and other Th2-skewing stimuli leads to dendritic cell activation and migration in vivo, but not in vitro. We are interested in learning the other cells and other pathways that specifically promote the activation and migration of Th2-skewing dendritic cells in response to allergens.
The role of innate accessory cells in Th2-differentiation
Although certain dendritic cell subsets have been shown to be essential for Th2-differentiation, they do not appear to be sufficient for Th2-differentiation. Dendritic cells have not been shown to secrete the stereotypical Th2-skewing cytokine, IL-4. Although other skewing signals have been implicated, the identity and source of the Th2-skewing signal remains unclear. With the goal of identifying novel therapeutics, we are interested in identifying novel accessory cells and signals involved in Th2-differentiation.
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