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

Cell. 2019 Feb 21;176(5):982-997.e16. doi: 10.1016/j.cell.2018.12.031. Epub 2019 Jan 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Cytokines / metabolism
  • Epithelium / immunology
  • Hair Follicle / metabolism
  • Hair Follicle / microbiology
  • Immunity, Innate
  • Interleukin-7 / metabolism
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology
  • Receptors, CCR6 / metabolism
  • Receptors, Notch / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Sebaceous Glands / immunology
  • Sebaceous Glands / metabolism*
  • Sebaceous Glands / microbiology*
  • Skin / metabolism
  • Skin Physiological Phenomena
  • Symbiosis
  • Thymic Stromal Lymphopoietin


  • CCR6 protein, mouse
  • Cytokines
  • Interleukin-7
  • Receptors, CCR6
  • Receptors, Notch
  • Receptors, Tumor Necrosis Factor
  • Thymic Stromal Lymphopoietin