Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium

Abstract

SUMMARY Immune cells and epithelium form sophisticated barrier systems in symbiotic relationships with microbiota. Evidence suggests that immune cells can sense microbes through intact barriers, but regulation of microbial commensalism remain largely unexplored. Here, we uncovered spatial compartmentalization of skin-resident innate lymphoid cells (ILCs) and modulation of sebaceous glands by a subset of RORγt+ ILCs residing within hair follicles in close proximity to sebaceous glands. Their persistence in skin required IL-7 and thymic stromal lymphopoietin, and localization was dependent on the chemokine receptor CCR6. ILC subsets expressed TNF receptor ligands, which limited sebocyte growth by repressing Notch signaling pathway. Consequently, loss of ILCs resulted in sebaceous hyperplasia with increased production of antimicrobial lipids and restricted commensalism of Gram-positive bacterial communities. Thus, epithelia-derived signals maintain skin-resident ILCs that regulate microbial commensalism through sebaceous gland-mediated tuning of the barrier surface, highlighting an immune-epithelia circuitry that facilitates host-microbe symbiosis.

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

“…Another study demonstrated that Id2 expression in ILC3s was important for the generation of IL‐22, which maintained a healthy microbiota that exhibited early colonization resistance to Citrobacter rodentium . ILC3s in the skin were recently shown to control the growth of the sebaceous glands and consequently the release of antimicrobial lipids, enabling the establishment of a healthy skin microbiota …”

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

“…Furthermore, sebocytes have an immunomodulatory capacity 27,28 and can produce several lipids and peptides that have demonstrable antimicrobial properties. [29][30][31][32] Loss of these physiological functions of SGs might contribute to the pathogenesis of many skin diseases. 33 To identify the mechanisms that govern pathological processes relevant to acne and other SG-associated dermatoses, it is imperative to understand the mechanisms underlying SG homeostasis.…”

Severe dysregulation of TNF expression leads to multiple inflammatory diseases and embryonic death

“…The increase in the size of sebaceous glands and the associated oily-looking fur in TNFdel4 and TNFdel4del5 mice is rather surprising since it was not observed in TNFDARE, BPSM1 and TNFdel4del6 mice. A recent report indicated that sebaceous gland homeostasis was regulated by a population of innate lymphoid cells (ILCs) residing within hair follicles in close proximity to the glands (19). These RORgt+ ILCs were found to negatively regulate sebaceous gland function by expressing TNF and lymphotoxins LTa3 and LTa1b2, which downregulated Notch signaling.…”