Publications by authors named "Brandon L Walling"

4 Publications

  • Page 1 of 1

Protean Regulation of Leukocyte Function by Nuclear Lamins.

Trends Immunol 2021 Apr 27;42(4):323-335. Epub 2021 Feb 27.

Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD 20892, USA. Electronic address:

The leukocyte nucleus must be sufficiently elastic to squeeze through tissue barriers during migration, but not so collapsible as to risk damaging chromatin. The proper balance is struck in part by the composition of the nuclear lamina, a flexible meshwork composed mainly of intermediate filaments woven from type A and type B lamin proteins, that is located subjacent to the inner nuclear membrane. There is now increasing evidence that, in addition to influencing nuclear shape and stiffness and cell migration, lamins and lamin-interacting proteins may also interact functionally with chromatin to influence leukocyte gene expression, differentiation, and effector function, including T cell differentiation, B cell somatic hypermutation, and the formation of neutrophil extracellular traps (NETosis).
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http://dx.doi.org/10.1016/j.it.2021.02.005DOI Listing
April 2021

Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites.

Immunity 2019 08 6;51(2):298-309.e6. Epub 2019 Aug 6.

David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address:

T-helper (Th) cell differentiation drives specialized gene programs that dictate effector T cell function at sites of infection. Here, we have shown Th cell differentiation also imposes discrete motility gene programs that shape Th1 and Th2 cell navigation of the inflamed dermis. Th1 cells scanned a smaller tissue area in a G protein-coupled receptor (GPCR) and chemokine-dependent fashion, while Th2 cells scanned a larger tissue area independent of GPCR signals. Differential chemokine reliance for interstitial migration was linked to STAT6 transcription-factor-dependent programming of integrin αβ expression: Th2 cell differentiation led to high αβ expression relative to Th1 cells. Th1 and Th2 cell modes of motility could be switched simply by manipulating the amount of αβ on the cell surface. Deviating motility modes from those established during differentiation impaired effector function. Thus, programmed expression of αβ tunes effector T cell reliance on environmental cues for optimal exploration of inflamed tissues.
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http://dx.doi.org/10.1016/j.immuni.2019.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904228PMC
August 2019

LFA-1 in T Cell Migration and Differentiation.

Front Immunol 2018 3;9:952. Epub 2018 May 3.

Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United States.

Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration. With 24 integrin pairs having been discovered to date, integrins are defined not only by the composition of the heterodimeric pair but by cell-type specific expression and their ligands. Furthermore, integrins not only facilitate adhesion but also induce intracellular signaling and have recently been uncovered as mechanosensors providing additional complexity to the signaling pathways. Among several leukocyte-specific integrins, lymphocyte function-associated antigen-1 (LFA-1 or αβ; CD11a/CD18) is a key T cell integrin, which plays a major role in regulating T cell activation and migration. Adhesion to LFA-1's ligand, intracellular adhesion receptor 1 (ICAM-1) facilitates firm endothelium adhesion, prolonged contact with antigen-presenting cells, and binding to target cells for killing. While the downstream signaling pathways utilized by LFA-1 are vastly conserved they allow for highly disparate responses. Here, we summarize the roles of LFA-1 and ongoing studies to better understand its functions and regulation.
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http://dx.doi.org/10.3389/fimmu.2018.00952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943560PMC
July 2019

A novel intracellular pool of LFA-1 is critical for asymmetric CD8 T cell activation and differentiation.

J Cell Biol 2017 11 27;216(11):3817-3829. Epub 2017 Sep 27.

Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY

The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8 T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells. The daughter CD8 T cells with disparate LFA-1 expression showed different patterns of migration on ICAM-1, APC interactions, and tissue retention, as well as altered effector functions. In addition, we identified Rab27 as an important regulator of the intracellular LFA-1 translocation. Collectively, our data demonstrate that an intracellular pool of LFA-1 in naive CD8 T cells plays a key role in T cell activation and differentiation.
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http://dx.doi.org/10.1083/jcb.201609072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674876PMC
November 2017