IL-7 Signaling on IL7Rα DCs Regulates the Naïve CD4 Niche Controlling Homeostatic Peripheral Expansion. Nature Immunology

IL-7 has been proposed as a primary driver of homeostatic peripheral expansion (HPE) occurring in response to lymphopenia. We show here that systemic IL-7 levels rise during lymphopenia due to diminished IL-7 utilization, and that this milieu supports HPE of CD8+, but not CD4+ T cells. Rather, HPE of CD4+ T cells requires IL-7 production by Class II+ dendritic cells, which co-express IL7R! (IL7R!DCs). Elevated stroma derived IL-7 in lymphopenic hosts paradoxically diminishes IL-7 production and Class II expression by IL7R!DCs via an IL-7R!, "C, STAT5 dependent feedback loop, diminishing support for CD4 HPE. This paradigm establishes IL7R!DCs as primary regulators of the peripheral CD4+ niche and explains the longstanding observation that lymphopenic humans undergoing HPE replenish CD8+ but not CD4+ T cell pools.