Postdoctoral researcher Tulane University School of Medicine New Orleans, Louisiana, United States
Introduction/Rationale: Pulmonary tissue injury caused by host dust mites, fungal products and parasitic helminth infections initiates Type 2 inflammation largely driven by TH2 and ILC2. Both lymphocyte populations secrete Type 2 cytokines like IL-4, 5, 9, 13 and Amphiregulin that drive a myriad of effector mechanisms TH2 cells were considered solely capable of memory Type 2 responses, but, ILC2 have also been shown to function independently of T and B lymphocytes for recall Type 2 inflammation incited by allergen challenge. Thus, a clear distinction between the functions of ILC2 and TH2 cells in the context of pathogen resistance and/or tissue repair remains unclear.
Methods: This study employed temporal CD4 depletion, selective ILC2 deficiency, adoptive transfer and pharmacological approaches to decipher the roles of TH2 vs. ILC2 subsets during anamnestic immunity against Nippostrongylus brasiliensis
Results: CD4 depletion prior to re-challenge had marginal effects, but constitutive CD4 depletion abrogated protective Type 2 immunity. Constitutive ILC2 deficiency impaired lung TH2 cell expansion and larval killing during secondary challenge, marked by exacerbated lung hemorrhage and increased IL-17+ gdT cell responses. Trained lung nILC2 and iILC2 subsets elicited by Nb rechallenge increased their expression of genes involved in glycolytic and oxphos metabolism and Tryptophan hydroxylase1 (Tph1) relative to primary lung ILC2. Critically, our data generated from gain and loss of function strategies demonstrated that lung serotonin production was ILC2-dependent and that serotonin prevented lung hemorrhage and IL-17+gdT cell responses irrespective of pathogen load.
Conclusion: Thus, while TH2 cells and ILC2s have interdependent functions upon initial antigen encounter, trained ILC2 distinctly produce serotonin for lung tissue repair and suppression of IL-17 dominant inflammation.
