Publications by authors named "Rosemary E Morman"

3 Publications

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The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude.

J Exp Med 2021 Jun;218(6)

Department of Pathology, Committees on Immunology and Cancer Biology, The University of Chicago, Chicago, IL.

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-γ production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses.
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http://dx.doi.org/10.1084/jem.20202032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056751PMC
June 2021

A Mouse Model for the Study of SYK Function through Chemical Genetics Demonstrates SYK-Dependent Signaling through the B Cell Receptor, but Not TLR4.

Immunohorizons 2019 07 1;3(7):254-261. Epub 2019 Jul 1.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907;

The SYK protein-tyrosine kinase is a well-known mediator of signals elicited by the clustering of BCR complexes and other receptors that bear components that contain one or more ITAM sequences. Additional roles for the kinase in signaling through other receptor classes also have been described. To assist in the identification of SYK-regulated processes, we developed mice lacking endogenous genes but containing instead genes coding for an analogue-sensitive form of SYK (SYK-AQL). SYK-AQL supports the development of B cells, and these can be activated with both anti-IgM F(ab') through the BCR and LPS through TLR4. An orthogonal inhibitor that selectively targets SYK-AQL blocks the activation of B cells by anti-IgM F(ab') in SYK-AQL-expressing but not wild-type cells. The SYK-AQL-specific inhibitor, however, does not block B cell activation in response to LPS in either wild-type or SYK-AQL-expressing cells. Thus, SYK is essential for coupling the BCR but not TLR4 to the activation of B cells.
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http://dx.doi.org/10.4049/immunohorizons.1800084DOI Listing
July 2019

BATF regulates the expression of Nfil3, Wnt10a and miR155hg for efficient induction of antibody class switch recombination in mice.

Eur J Immunol 2018 09 26;48(9):1492-1505. Epub 2018 Jun 26.

Department of Biological Sciences and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, USA.

BATF functions in T cells and B cells to control the host response to antigen and promote the production of class switched immunoglobulins. In this study, we demonstrate that BATF expression increases rapidly, and transiently, following B cell stimulation and use an inducible murine model of BATF deletion to show that this induction is necessary, and sufficient, for immunoglobulin (Ig) class switch recombination (CSR). We examine two genes (Nfil3 and miR155gh) that are positively regulated, and one gene (Wnt10a) that is negatively regulated by BATF during CSR. These genes play essential roles in CSR and each impacts the expression and/or function of the others. Our observations allow these targets of BATF regulation to be positioned in a network upstream of the activation of germline transcripts (GLT) from the IgH locus and of transcriptional activation of Aicda - the gene encoding the enzyme directing Ig gene rearrangements. This work extends the knowledge of the molecular control of CSR and, importantly, positions the induction and function of BATF as an early event in this process.
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http://dx.doi.org/10.1002/eji.201747360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357966PMC
September 2018