Swirski focuses on understanding how
leukocytes shape and are shaped by inflammation. His research uses
in vivo models of acute and chronic inflammation relevant to cardiovascular,
neurodegenerative, infectious, and metabolic diseases.
Novel findings Monocytes and macrophages • Swirski described that increased blood
monocyte levels, otherwise known as monocytosis, develop in response to
hypercholesterolemia and is progressive and proportional to disease severity. • Although monocytes develop predominantly in bone marrow, Swirski showed that
hypercholesterolemia leads to monocyte production in the spleen in a process called
extramedullary hematopoiesis, which further drives
atherosclerosis progression. • Showed that monocyte-derived macrophages recruited to the atherosclerotic plaque self-renew in the lesion, further accelerating atherosclerosis. and showed a role for a splenic monocyte reservoir as a source of monocytes after myocardial infarction.
Lifestyle and brain-body communication • Swirski explores how cardiovascular health is affected by diet, sleep, exercise, and other lifestyle patterns. He showed that sleep limits monocyte production, thereby protecting against atherosclerosis. • He demonstrated that sleep interruption increases the rate of
hematopoiesis in the bone marrow, which accelerates
neutral drift. • Showed that IL-3 is a crucial communicator between glial cells (
microglia) located throughout the brain and spinal cord, and
astrocytes. Using mouse models of
Alzheimer’s Disease (AD), data showed that IL-3 protects against AD by programming microglia. • Under psychological stress, neurons from different brain regions control the migration of immune cells in the body. Mice under stress were more prone to higher inflammation and death in response to infection with influenza and SARS-CoV-2. • Fasting in mice prompts monocytes to re-enter the bone marrow, which increases their lifespan. This process is mediated by the
hypothalamic-pituitary-adrenal axis (HPA). Upon re-feeding, distinct monocytes mobilize back to the blood, altering the host's response to infection. The underlying study showed the body can limit energy expenditure when nutrition is scarce. Without it, the body slows down metabolic expenditure, limiting production and preserving—and thus extending—the lifespan of already-made, short-lived monocytes.
Immunometabolic communication • Swirski identified an on-demand mechanism by which transient monocyte-derived macrophages dispose of
erythrocytes and recycle iron. • Identified a population of intraepithelial
T cells that are strategically positioned in the gut that modulate systemic dietary metabolism. Without these, mice were metabolically hyperactive, and resisted the development of obesity, hypertension, diabetes, and hypercholesterolemia/atherosclerosis. • Showed that cholesterol sensors called
Liver X Receptors were important in developing and functioning T cells in the
thymus, the lymphoid gland where T cells are produced.
Influence of hematopoietic growth factors • Swirski showed the influence of growth factors in disease, where he described a GM-CSF-producing
B cell that protects against sepsis and
pneumonia. • Demonstrated that the growth factor
interleukin 3 (IL-3) aggravates sepsis by eliciting a
cytokine storm, heightening inflammation leading to death. • Identified a critical role for IL-3 in myocarditis and showed that IL-3 regulates
microglial function in
Alzheimer’s Disease. == Honors and awards ==