Dietary tryptophan deficiency promotes gut RORγt+ Treg cells at the expense of Gata3+ Treg cells and alters commensal microbiota metabolism.

Micronutrient deficiency is a major cause of disease throughout the world. Yet, how perturbations influence the immune-microbiome interface remains poorly understood. Here, we report that loss of dietary tryptophan (Trp) reshapes intestinal microbial communities, including the depletion of probiotic L. reuteri, drives transcriptional changes to immune response genes in the intestinal ileum, and reshapes the regulatory T cell (Treg) compartment. Dietary Trp deficiency promotes expansion of RORγt+ Treg cells and the loss of Gata3+ Tregs in a microbiota-dependent manner. In the absence of dietary Trp, provision of the AhR ligand indole-3-carbinol is sufficient to restore the Treg compartment. Together, these data show that dietary Trp deficiency perturbs the interaction between the host and its bacterial symbionts to regulate Treg homeostasis via the deprivation of bacterially derived Trp metabolites. Our findings highlight an essential role for immune-microbiome crosstalk as a key homeostatic regulator during nutrient deficiency.

Regulation of the alveolar regenerative niche by amphiregulin-producing regulatory T cells.

Following respiratory viral infection, regeneration of the epithelial barrier is required to preserve lung function and prevent secondary infections. Lung regulatory T (Treg) cells are critical for maintaining blood oxygenation following influenza virus infection through production of the EGFR ligand amphiregulin (Areg); however, how Treg cells engage with progenitors within the alveolar niche is unknown. Here, we describe local interactions between Treg cells and an Areg-responsive population of Col14a1+EGFR+ lung mesenchymal cells that mediate type II alveolar epithelial (AT2) cell-mediated regeneration following influenza virus infection. We propose a mechanism whereby Treg cells are deployed to sites of damage and provide pro-survival cues that support mesenchymal programming of the alveolar niche. In the absence of fibroblast EGFR signaling, we observe impaired AT2 proliferation and disrupted lung remodeling following viral clearance, uncovering a crucial immune/mesenchymal/epithelial network that guides alveolar regeneration.

Glycans for good.

The gut commensal bacterium Bifidobacterium bifidum promotes immune tolerance by facilitating the induction of colonic regulatory T cells.