Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition

Nat Immunol. 2020 Oct;21(10):1181-1193. doi: 10.1038/s41590-020-0753-y. Epub 2020 Aug 17.

Abstract

Type 2 cytokine responses promote parasitic immunity and initiate tissue repair; however, they can also result in immunopathologies when not properly restricted. Although basophilia is recognized as a common feature of type 2 inflammation, the roles basophils play in regulating these responses are unknown. Here, we demonstrate that helminth-induced group 2 innate lymphoid cell (ILC2) responses are exaggerated in the absence of basophils, resulting in increased inflammation and diminished lung function. Additionally, we show that ILC2s from basophil-depleted mice express reduced amounts of the receptor for the neuropeptide neuromedin B (NMB). Critically, NMB stimulation inhibited ILC2 responses from control but not basophil-depleted mice, and basophils were sufficient to directly enhance NMB receptor expression on ILC2s. These studies suggest that basophils prime ILC2s to respond to neuron-derived signals necessary to maintain tissue integrity. Further, these data provide mechanistic insight into the functions of basophils and identify NMB as a potent inhibitor of type 2 inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / immunology*
  • Cell Communication
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunity, Innate
  • Lung / metabolism*
  • Lung / pathology
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurokinin B / analogs & derivatives
  • Neurokinin B / metabolism
  • Nippostrongylus / physiology*
  • Strongylida Infections / immunology*
  • Th2 Cells / immunology
  • Tryptases / genetics

Substances

  • Cytokines
  • Neurokinin B
  • neuromedin B
  • Mcpt8 protein, mouse
  • Tryptases