Ari Molofsky, MD, PhD

Assistant Professor
Department of Laboratory Medicine

Westernized societies are experiencing an epidemic of obesity. Obesity promotes local inflammation in visceral adipose tissue that leads to systemic inflammation, insulin resistance, and the development of type 2 diabetes. However, the function and regulation of normal immune cells in healthy adipose tissue is poorly understood. Allergic, type 2 immune cells are surprisingly abundant in healthy, lean adipose tissue and are co-regulated to maintain metabolic health and limit obesity induced inflammation and insulin resistance. These findings suggest allergic immunity, traditionally associated with pathology (asthma, atopy, allergy) as well as protection from multicellular helminthic worms, also plays a central role in the normal physiologic regulation of metabolism, and may participate more broadly in tissue homeostasis and repair.

Our laboratory studies the allergic immune module in adipose tissue during conditions of metabolic health, obesity, and post infection with helminths, bacteria, or viruses. We are focused on the regulation, interactions, cytokine production, and metabolic impact of the cells in this allergic module, including group 2 innate lymphoid cells (ILC2), eosinophils, alternatively activated macrophages, and tissue regulatory T (Treg) cells. We anticipate this knowledge will accelerate the development of human therapeutics that can restore balanced anti-inflammatory, allergic-type immune responses that decline in adipose tissue with obesity and old age, limiting the progression of insulin resistance and type 2 diabetes. Our group’s long-terms goals are to understand the impact of the allergic immune module in a range of metabolic tissues, infectious and autoimmune models, and human disease.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Research Summary: 
Type 2 immunity in metabolic health and disease

Websites

Featured Publications: 

Interleukin-33 and Interferon-? Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation.

Immunity

Molofsky AB, Van Gool F, Liang HE, Van Dyken SJ, Nussbaum JC, Lee J, Bluestone JA, Locksley RM

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation.

Immunity

Molofsky AB, Savage AK, Locksley RM

Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages.

The Journal of experimental medicine

Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM

Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis.

Science (New York, N.Y.)

Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM

Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.

The Journal of experimental medicine

Molofsky AB, Byrne BG, Whitfield NN, Madigan CA, Fuse ET, Tateda K, Swanson MS