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. Overall design: 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.