PD-1 expression affects cytokine production by ILC2 and is influenced by peroxisome proliferator-activated receptor-?.

ABSTRACT: INTRODUCTION:Innate lymphoid cells (ILCs) can provide early cytokine help against a variety of pathogens in the lungs and gastrointestinal tract. Type 2 ILC (ILC2) are comparable to T helper 2 cells found in the adaptive immune system, which secrete cytokines such as interleukin 5 (IL-5) and IL-13 and have been found to play roles in host defense against helminth infections and in allergic responses. Recent studies have identified that programmed cell death protein 1 (PD-1) and peroxisome proliferator activated receptor-? (PPAR-?) are highly expressed by ILC2. We examined whether PD-1 plays a role in ILC2 function and whether there was any connection between PD-1 and PPAR-? METHODS: To ensure that only innate immune cells were present, ILC2 cells were examined from RAG1-/- and PD-1-/- xRAG1-/- mice under steady-state or following inoculation with IL-33. We also tested ILC2 generated from bone marrow of RAG1-/- and PD-1-/- xRAG1-/- mice for their production of cytokines. These in vitro-derived ILC2 were also exposed to agonist and antagonist of PPAR-?. RESULTS:We found that ILC2 from PD-1-/- xRAG1-/- mice had reduced frequencies of IL-5 and IL-13 producing cells both in vitro upon IL-33 stimulation and in vivo following intraperitoneal administration of IL-33 when compared with ILC2 from RAG1-/- mice. However, by adding IL-2, IL-25, and thymic stromal lymphopoietin to the in vitro cultures, the frequency of IL-5 and IL-13 expressing ILC2 from PD-1-/- xRAG1-/- mice became similar to the frequency observed for ILC2 from RAG1-/- mice. In addition, PPAR-? agonists and antagonists were found to increase and decrease PD-1 expression on ILC2 respectively. CONCLUSIONS:These findings illustrate that chronic loss of PD-1 plays a role in ILC2 function and PD-1 expression can be modulated by PPAR-?.

SUBMITTER: Batyrova B 

PROVIDER: S-EPMC7016838 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature