<p>Benign prostatic hyperplasia (BPH) is a common urologic
condition among older men, affecting approximately half of men by age 50 and
nearly 80% by age 80. Lower urinary
tract symptoms (LUTS) associated with BPH may significantly impact quality of
life for many of these men. Inflammation
has been associated with the development and progression of BPH however, the
precise impact and role(s) of immune cells in these conditions remains
unclear. Many previous studies over the
decades have explored the roles of immune cells in prostate disease in animal
models and prostate tissues from human patients, and, more recently, through
transcriptomic analyses of bulk cell populations and of single cells. These and
other emerging technologies continue to add to the body of knowledge related to
this area.</p>
<p>The prostate is a complex organ composed of multiple
epithelial and mesenchymal cell types and subtypes. The growth, morphology, and function of these
cells is influenced by autocrine and paracrine cell-cell interactions in ways that
are largely not yet understood. A better
understanding of the composition, heterogeneity, morphology, interactions, and
functional features of various prostate cell types, particularly involving
immune cells in the context of inflammatory processes, is expected to improve
our understanding of the impact of altered cellular composition and
communication on prostate homeostasis and disease.</p>
<p>Inflammation has been shown to impact the growth,
morphology, and function of various prostate cell types. It is hypothesized
that inflammation promotes epithelial cell proliferation and differentiation in
BPH despite androgen-targeted therapy. It
is hypothesized that communications between and within various immune cell
populations perpetuate the non-resolving inflammatory microenvironment that
promotes prostate cell expansion. In
this research, the POET-3 mouse model of inducible autoimmune inflammation is
used to evaluate the impact of autoimmune-type inflammation on basal epithelial
cell progenitor growth and differentiation in the absence of androgens mimicking
the conditions of androgen deprivation therapy (ADT), and to demonstrate the
enhanced growth and differentiation potential conferred on basal progenitors by
inflammation. </p>
<p>Additionally, this research evaluates the morphology, gene
expression, and cell-cell interaction predictions of BPH prostate immune cells to
explore the role of immune cells and their interactions in driving BPH
inflammation. </p>
<p>Overall, inflammation induced epithelial and stromal
expansion and basal progenitor cell proliferation in vivo and promoted basal
progenitor cell growth and differentiation in vitro under androgen-deficient
conditions mimicking androgen-targeted therapy.
Histologic evaluation of BPH specimens reveals the composition and distribution
of immune cells, including organizing lymphoid structures resembling tertiary
lymphoid structures (TLS). Also,
analyses of single cell RNA sequencing data of gene expression patterns and
signaling pathways reveal a mixed inflammatory microenvironment in BPH. Furthermore, predicted ligand-receptor
interactions indicate mixed inflammatory signaling between and among immune
cell populations, including T cells, macrophages, and mast cells, that likely
to the unresolving nature of BPH inflammation.</p>
<p>In all, the results of these studies demonstrate inflammation-induced
epithelial and stromal expansion in a mouse model of resolving prostatitis and
indicate potential roles for multiple immune cell populations and their
interactions in driving the ongoing inflammation of BPH, suggesting that this
ongoing inflammation may impact the progressive stromal and epithelial
expansion characteristic of BPH. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/15067305 |
| Date | 28 July 2021 |
| Creators | Meaghan M Broman (11192163) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/Inflammation_and_Benign_Prostatic_Hyperplasia_Role_of_immune_cells_and_their_interactions_in_chronic_inflammation_and_cellular_hyperplasia/15067305 |
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