Fundamental to immune-mediated protection is the ability of leukocytes to survey barrier surfaces and quickly respond to infection or tissue damage. Signals from cytokines, chemokines and cells (immune and stromal) within the tissue provide critical cues for T cell migration at sites of inflammation, but the mechanics of T cell motility to these signals is poorly understood. Our overall goal is to define mechanistic control points for T cell surveillance within functionally distinct sites of inflammation. In the long-term, identification of diverse requirements for T cell function will lead to the selective therapeutic targeting of specific tissues or pathologies. Inflammation results in a change in both the architecture of the tissue as well as its composition. Using intravital multiphoton microscopy of inflamed tissues, we find that interstitial T cell motility in the inflamed skin is highly dependent on alpha-v integrin. Blockade or genetic knock-down of alpha-v halts T cell interstitial movement and also attenuates effector function. We hypothesize that T cell-matrix interactions are critical for lymphocyte surveillance of the inflamed tissue for efficient location of APCs necessary for activation of effector function. The inflamed tissue is highly complex and the efficiency and mode of surveillance will likely differ with the local array of cytokines, chemokines and cellular infiltrate. We have identified two likely modifiers of T cell motility: 1) the microstructure of collagen fibers and 2) the effector lineage of the infiltrating CD4+ T cell.
Aim 1. Role of av-integrins in effector T cell surveillance in the inflamed dermis.
Aim 2. Modes of T cell motility in distinct inflammatory environments.
Aim 3. Functionally distinct effector T cell activity in inflammation. Effector T cells function to eradicate pathogens but also contribute to immunopathologies. By identifying key parameters for T cell effector activity in the inflamed dermis we will inform new inflammation-specific therapies.

Public Health Relevance

Activated effector T cells traffic to inflamed tissues where they scan and locate damaged or infected cells: beneficial for pathogen clearance but pathogenic in autoimmune/inflammatory diseases. Our goal is to, define mechanistic control points for T cell surveillance within functionally distinct inflammatory sites. Identification of diverse requirements for T cell function will lead to selective therapies for specific tissues or pathologies.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-LGR-I (J1))
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University of Rochester
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Capece, Tara; Walling, Brandon L; Lim, Kihong et al. (2017) A novel intracellular pool of LFA-1 is critical for asymmetric CD8+ T cell activation and differentiation. J Cell Biol 216:3817-3829
Reilly, Emma C; Lambert-Emo, Kris; Topham, David J (2016) The Effects of Acute Neutrophil Depletion on Resolution of Acute Influenza Infection, Establishment of Tissue Resident Memory (TRM), and Heterosubtypic Immunity. PLoS One 11:e0164247
Gaylo, Alison; Overstreet, Michael G; Fowell, Deborah J (2016) Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis. J Vis Exp :e53585
Lambert Emo, Kris; Hyun, Young-Min; Reilly, Emma et al. (2016) Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen. PLoS Pathog 12:e1005881
Surve, Chinmay R; To, Jesi Y; Malik, Sundeep et al. (2016) Dynamic regulation of neutrophil polarity and migration by the heterotrimeric G protein subunits G?i-GTP and G??. Sci Signal 9:ra22
Gaylo, Alison; Schrock, Dillon C; Fernandes, Ninoshka R J et al. (2016) T Cell Interstitial Migration: Motility Cues from the Inflamed Tissue for Micro- and Macro-Positioning. Front Immunol 7:428
Billroth-MacLurg, Alison C; Ford, Jill; Rosenberg, Alexander et al. (2016) Regulatory T Cell Numbers in Inflamed Skin Are Controlled by Local Inflammatory Cues That Upregulate CD25 and Facilitate Antigen-Driven Local Proliferation. J Immunol 197:2208-18
Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris et al. (2015) Neutrophil trails guide influenza-specific CD8? T cells in the airways. Science 349:aaa4352
Tankam, Patrice; He, Zhiguo; Chu, Ying-Ju et al. (2015) Assessing microstructures of the cornea with Gabor-domain optical coherence microscopy: pathway for corneal physiology and diseases. Opt Lett 40:1113-6
Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris et al. (2015) Visualization of integrin Mac-1 in vivo. J Immunol Methods 426:120-7