Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion

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.

Epithelial-Cell-Derived Cytokines in Patients with Obesity before and after Bariatric Surgery

“…In the murine model, it has been found that TSLP overexpression caused WAT loss by inducing skin T-cell migration and increasing sebum hypersecretion. WAT loss was independent of ILCs2, eosinophils, and T reg cells [23].…”

Thymic stromal lymphopoietin controls hair growth

“…Our immunostaining suggests that keratinocytes are not the sole source of TSLP during homeostatic hair cycle and wounding healing and that additional immune and non-immune cells in the dermis contribute to local TSLP production. Emerging evidence has delineated TSLP functions in airway epithelial cell migration ( Kabata et al., 2020 ), T Reg expansion ( Leichner et al., 2017 ), innate lymphoid cell activation ( Kim et al., 2013 ), and sebaceous gland activity ( Choa et al., 2021 ). We expect that TSLP exhibits pleiotropic activity beyond the known functions in the skin and other tissues.…”

Alarmin Cytokines as Central Regulators of Cutaneous Immunity

“…Endogenous TSLP controls the steady-state level of sebum secretion and sebum-associated antimicrobial peptide expression through the activation of T cells in murine skin. TSLP overexpression results in loss of white adipose tissue in conjunction with sebum hypersecretion ( 18 ). TSLP helps to maintain skin-resident RORγt + ILCs within hair follicles, and, by the virtue of their location, ILCs negatively regulate surrounding sebaceous gland size and lipid content to regulate commensal bacteria equilibrium and fine-tune the skin barrier surface in mice ( 198 ).…”

“…A diverse range of immune cell types, including several T cell subsets, macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), and mast cells, is localized around vasculature and extracellular matrix proteins in the dermis ( 14 – 16 ). This complex network of dermal immune cells helps in many aspects of host physiology, including protection against pathogens, wound healing ( 17 ), sebum production ( 18 ), and hair follicle homeostasis ( 19 ).…”