Intestinal Lin-c-Kit+NKp46-CD4- population highly produces IL-22 upon IL-1β stimulation (P3260)

Abstract Small intestinal innate lymphoid cells (ILCs) regulate intestinal epithelial cell homeostasis and prevent pathogenic bacterial infections by producing IL-22. NKp46+ ILC (ILC22) and CD4+ ILC (CD4+ LTi) are known as main sources for IL-22 in the small intestine. We found that Lin-c-Kit+NKp46-CD4- (CD4- LTi), ILC22, and CD4+ LTi cells comprised 0.30 ± 0.03%, 1.10 ± 0.12%, and 0.07 ± 0.01%, respectively, of the total lymphocytes in the small intestinal lamina propria of adult mice (BALB/c). We next compared the induction of IL-17F and IL-22 among CD4- LTi, ILC22, and CD4+ LTi cells under stimulation with IL-1β or IL-23 or IL-1β and IL-23 stimulation, by real-time PCR, Bio-Plex analysis, and intracellular staining. We found here that CD4- LTi cells that expressed RORγt and IL-7Rα strongly expressed the transcripts for Il17f and Il22, and produced the proteins for IL-17F and IL-22 after stimulation with IL-1β and IL-23 stimulation compared with ILC22 and CD4+ LTi cells. However, none of CD4- LTi, ILC22, and CD4+ LTi cells produced IL-17F and IL-22 after stimulation with Pam3CSK4 (TLR2 ligand), Poly(I:C) (TLR3 ligand), or LPS (TLR4 ligand) for 24 hrs. Taken together, these findings indicate that the Lin-c-Kit+NKp46-CD4- population may control intestinal homeostasis and provide intestinal protection by producing high levels of IL-17F and IL-22 under the stimulation with IL-1β and IL-23.