Btn2a2 Regulates ILC2-T Cell Cross Talk in Type 2 Immune Responses

Michael Frech, Yasunori Omata, Angelika Schmalzl, Stefan Wirtz, Leila Taher, Georg Schett, Mario M Zaiss, Kerstin Sarter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Innate lymphoid cells (ILC) not only are responsible for shaping the innate immune response but also actively modulate T cell responses. However, the molecular processes regulating ILC-T cell interaction are not yet completely understood. The protein butyrophilin 2a2 (Btn2a2), a co-stimulatory molecule first identified on antigen-presenting cells, has a pivotal role in the maintenance of T cell homeostasis, but the main effector cell and the respective ligands remain elusive. We analyzed the role of Btn2a2 in the ILC-T cell cross talk. We found that the expression of Btn2a2 is upregulated in ILC2 following stimulation with IL-33/IL-25/TSLP. In vitro and in vivo experiments indicated that lack of Btn2a2 expression on ILC2 resulted in elevated T cell responses. We observed an enhanced proliferation of T cells as well as increased secretion of the type 2 cytokines IL-4/IL-5/IL-13 following cocultures with Btn2a2-deficient ILC2. In vivo transfer experiments confirmed the regulatory role of Btn2a2 on ILC2 as Btn2a2-deficient ILC2 induced stronger T cell responses and prevented chronic helminth infections. Taken together, we identified Btn2a2 as a significant player in the regulation of ILC2-T cell interactions.

Original languageEnglish
Article number757436
Number of pages14
JournalFrontiers in Immunology
Publication statusPublished - 2022


  • butyrophilin
  • co-stimulation and co-inhibition receptors
  • helminth infection
  • ILC2
  • type 2 immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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