Intestinal inflammations increase efflux of innate lymphoid cells from the intestinal mucosa to the mesenteric lymph nodes through lymph-collecting ducts

Introduction: Innate lymphoid cells (ILCs) are abundant in the intestinal mucosa, forming boundaries externally. Herein, ILCs were directly obtained from intestinal lymph using a lymph fistula rat model and analyzed under physiological and pathological conditions.

Methods: Thoracic duct (TD) lymphocytes were collected by cannulation with/without preceded mesenteric lymphadenectomy, which were comparable to lymphocytes flowing through mesenteric lymphatic vessels (MLVs) or TD, respectively. The collected ILCs were classified according to gene transcription factors and analyzed by flow cytometry. The effect of IL-25 or indomethacin was studied.

Results: The proportion of total ILCs in the MLVs (MLV-ILCs) was significantly higher than that in TD (TD-ILCs, 0.01% vs. 0.003%, respectively). Physiologically, there were several significant differences in the MLV-ILCs compared with TD-ILCs, including the proportion of ILC2 (42.3% vs. 70.9%) and ILC3 (33.3% vs. 13.8%), and the proportion of α4-integrin-positive cells (36.8% vs. 0.3%). IL-25 significantly increased the proportion of MLV-ILC2 after 3 days. Indomethacin-induced intestinal injury increased the proportion of MLV-ILC3 in the early phase within 12 h.

Conclusion: Intestinal ILCs were found to migrate through MLVs. The altered mobilization of MLV-ILCs after stimuli suggests that ILCs play an important role in regulating the immune responses at the secondary lymph nodes.