Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion

Ruth Choa1, Junichiro Tohyama1, Shogo Wada2, Hu Meng3, Jian Hu4, Mariko Okumura1, Rebecca M May5, Tanner F Robertson1,6, Ruth-Anne Langan Pai1, Arben Nace7, Christian Hopkins7, Elizabeth A Jacobsen8, Malay Haldar1, Garret A FitzGerald3, Edward M Behrens9, Andy J Minn10, Patrick Seale11, George Cotsarelis7, Brian Kim12,13,14,15, John T Seykora7, Mingyao Li4, Zoltan Arany2, Taku Kambayashi16

  1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  2. Cardiovascular Institute and the Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  3. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  4. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  5. Arkana Laboratories, Little Rock, AR, USA.
  6. Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  7. Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  8. Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
  9. Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  10. Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  11. Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  12. Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  13. Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
  14. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  15. Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO, USA.
  16. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. taku.kambayashi@pennmedicine.upenn.edu.

Abstract

Emerging studies indicate that the immune system can regulate systemic metabolism. Here, we show that thymic stromal lymphopoietin (TSLP) stimulates T cells to induce selective white adipose loss, which protects against obesity, improves glucose metabolism, and mitigates nonalcoholic steatohepatitis. Unexpectedly, adipose loss was not caused by alterations in food intake, absorption, or energy expenditure. Rather, it was induced by the excessive loss of lipids through the skin as sebum. TSLP and T cells regulated sebum release and sebum-associated antimicrobial peptide expression in the steady state. In human skin, TSLP expression correlated directly with sebum-associated gene expression. Thus, we establish a paradigm in which adipose loss can be achieved by means of sebum hypersecretion and uncover a role for adaptive immunity in skin barrier function through sebum secretion.

Presented By Ruth Choa | ORCID iD

Immunology & Microbiology, MetabolismNicholas Liao2021-07 (Jul)