NIH VideoCast - Multicellular control of immunological homeostasis

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Multicellular control of immunological homeostasis

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Air date:	Wednesday, October 14, 2020, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 722 (111 Live, 611 On-demand)
Category:	Immunology
Runtime:	01:12:01
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	IIG Seminar Hari completed his Ph.D. in Cell Biology at the University of Toronto, Canada, where he employed single-molecule imaging techniques to study multimolecular interactions in individual immune cells. Specifically, he focused on how the dynamics of the actin cytoskeleton regulated receptor diffusion and immune cell signal transduction at fast timescales. In 2016, Hari joined Dr. Ron Germain’s lab at the NIH, seeking to understand how the immune response was regulated over much larger spatiotemporal scales. Here, Hari transitioned to studying multicellular systems and their emergent properties within complex tissue environments. His work to date has predominantly focused on the control of self-antigen specific T cells by regulatory T cells within murine secondary lymphoid organs. Using a combination of multiplexed tissue imaging, clear organ volume imaging, and computational modeling techniques, Hari was able to study physiological numbers of self-reactive T cells, dendritic cells, and regulatory T cells within unperturbed tissues — a level of in situ analysis that has not been reported to date. As a result, he uncovered an essential feedback control system that routinely constrains autoimmune T cell responses in secondary lymphoid organs, thereby maintaining immunological homeostasis. Such feedback control gives rise to a sharp discriminatory boundary (i.e. an emergent property) between self and non-self. Surprisingly, modest reductions (< two-fold) in critical parameters governing the system are sufficient to alter the discriminatory boundary, enabling some self-reactive T cells to escape control and become threats to the host. These findings help to explain why haploinsufficiency in specific genes, such as CTLA-4, can lead to human autoimmunity. Hari’s unique combination of interdisciplinary approaches makes his work of broad interest to immunologists as well as biologists from diverse disciplines. For more information go to https://www.niaid.nih.gov/research/immunology-interest-group

NLM Title:	Multicellular control of immunological homeostasis / Harikesh Wong.
Author:	Wong, Harikesh. National Institutes of Health (U.S.),
Publisher:
Abstract:	(CIT): IIG Seminar Hari completed his Ph.D. in Cell Biology at the University of Toronto, Canada, where he employed single-molecule imaging techniques to study multimolecular interactions in individual immune cells. Specifically, he focused on how the dynamics of the actin cytoskeleton regulated receptor diffusion and immune cell signal transduction at fast timescales. In 2016, Hari joined Dr. Ron Germain's lab at the NIH, seeking to understand how the immune response was regulated over much larger spatiotemporal scales. Here, Hari transitioned to studying multicellular systems and their emergent properties within complex tissue environments. His work to date has predominantly focused on the control of self-antigen specific T cells by regulatory T cells within murine secondary lymphoid organs. Using a combination of multiplexed tissue imaging, clear organ volume imaging, and computational modeling techniques, Hari was able to study physiological numbers of self-reactive T cells, dendritic cells, and regulatory T cells within unperturbed tissues -- a level of in situ analysis that has not been reported to date. As a result, he uncovered an essential feedback control system that routinely constrains autoimmune T cell responses in secondary lymphoid organs, thereby maintaining immunological homeostasis. Such feedback control gives rise to a sharp discriminatory boundary (i.e. an emergent property) between self and non-self. Surprisingly, modest reductions (< two-fold) in critical parameters governing the system are sufficient to alter the discriminatory boundary, enabling some self-reactive T cells to escape control and become threats to the host. These findings help to explain why haploinsufficiency in specific genes, such as CTLA-4, can lead to human autoimmunity. Hari's unique combination of interdisciplinary approaches makes his work of broad interest to immunologists as well as biologists from diverse disciplines.
Subjects:	Homeostasis--immunology T-Lymphocytes, Regulatory--immunology
Publication Types:	Lecture Webcast

NLM Classification:	QW 568
NLM ID:	101773039
CIT Live ID:	38840
Permanent link:	https://videocast.nih.gov/watch=38840

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