PD-1 signaling in intestinal lymphoid tissue inducer cells facilitates gut homeostasis

PD-1/PD-L1 signaling play inhibiting role in CD4+ effector T cells. Innate lymphoid cells (ILCs) represent the innate counterparts of the CD4+ T helper cells, the role of PD-1/PD-L1 signaling on ILCs is still need more study. We found high PD-1 expression on Lymphoid tissue inducer (LTi) cells by experiment. RNA-sequencing analysis suggests different gene expression feature in the PD-1high and PD-1- LTi cells from Pdcd1hu/+ or Pdcd1hu/- mice. PD-1-expressing LTi are more prominent in cytokine production and Pdcd1 deficit could downregulate LTi cytokine production. In addition, metabolic pathways analysis showed the most dramatic downstream change of PD-1 signaling was from lipid metabolism-related genes. Thus, PD-1/PD-L1 signaling promotes LTi effector function and the mechanism may through regulating lipid metabolism. Meanwhile, the RNA-seq data of LTi cultured in presence or absence of palmitic acid also revealed the regulatory function of fatty acid oxidation on LTi. Meanwhile, the RNA-seq data of LTi cultured in presence or absence of palmitic acid also revealed the regulatory function of fatty acid oxidation on LTi. We want to identify unique genes expressed by PD-1high LTi and PD-1- LTi from Pdcd1hu/+ and Pdcd1hu/- mice with RNA-Seq, and to identify gene expression changes between LTi cultured in presence or absence of palmitic acid with RNA-Seq. To further investigate the relationship between activation and metabolism, we conducted sc-RNA-Seq experiment with all ILCs and retained ILC3s (Nkp46+ ILC3 and LTi) for downstream analysis.