Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells whose
immunosuppressive activities contribute to cancer and other diseases. MDSCs
appear to increase with age, and this presumably contributes to immunosuppression
and the increased incidence of certain diseases. Why MDSCs increase with
age is not entirely clear. Herein we present evidence that MDSC expansion is due
in part to age-related changes in hematopoiesis, including the acquisition of
mutations that favor myelopoiesis, which are compounded by changes in the
aging microenvironment that favor the production of MDSCs.
Dr. Dawn Bowdish and her PhD student Dessi Loukov collaborated with Dr. Monica Maly and Sara Karampatos (Rehabilitation Science) and found that monocytes were more activated and pro-inflammatory in women with osteoarthritis, and that elevated inflammation and body mass index were associated with increased monocyte activation. Further, the team found that women with osteoarthritis and more activated monocytes experienced worse pain than individuals with less activated monocytes. These findings highlight the importance of modulating inflammation and body mass to manage osteoarthritis and open up new avenues for therapeutic research.
Read the full publication in the Osteoarthritis Research Society International (OARSI) Journal
As featured in Eureka Alert: https://www.eurekalert.org/pub_releases/2017-11/mu-rul112717.php
We’re thrilled that our publication was featured as an editorial in Cell Host & Microbe. Read Drs Erin S. Keebaugh and William W. Ja’s excellent editorial here…..
PhD student Dessi Loukov in the lab of Dr. Dawn Bowdish, recently published a study showing that splenomegaly in old mice is a result of extramedullary hematopoiesis, and that this increased monopoiesis is driven by age-associated increase in TNF. The study compared changes in the microarchitecture and composition of the spleen in old and young mice and found that in old mice, there was an increase in the size and cellularity of the red pulp (the site of hematopoiesis of myeloid precursors). To study the role of TNF in the development of extramedullary hematopoiesis, they used TNF KO mice and found that these mice did not have increased extramedullary monopoiesis. Furthermore, they demonstrated that increased splenic myelopoiesis was a result of the aging microenvironment. This work suggests that strategies which aim to decrease the inflammatory microenvironment that comes with aging, would be effective in reducing inflammatory diseases propagated by cells of the myeloid lineage. Read More
Colonization of Streptococcus pneumoniae within the upper respiratory tract (URT) of elderly individuals is a major concern, as it often results in the development of pneumonia, which can be deadly in this population. A study published by MIRC Masters’ student Netusha Thevaranjan, under the supervision of Dr. Dawn Bowdish, examined how aging can change the composition of the respiratory microbial community and consequently, impact bacterial colonization. Using a mouse model of pneumococcal colonization, the study characterized the composition of the URT microbiota in young, middle-aged, and old mice in both the naïve state, and throughout the course of nasopharyngeal colonization with S. pneumoniae. It was shown that the composition of the URT microbiota differs with age, and that colonization with S. pneumoniae in older mice disrupted pre-existing microbial communities.
Furthermore, the study demonstrated that there were several interspecies interactions between S. pneumoniae and resident microbes. In particular,Streptococcus interacted competitively with Staphylococcus and synergistically with Haemophilus. This work provides insight into how aging influences bacterial colonization, and understanding the relationship between these two factors can help create strategies to protect the elderly from age-associated infections and disease. Read More
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