UCSF

CD169+ subcapsular sinus macrophages (SSMs) line the capsule of the lymph node and have important roles in antigen capture and display. To better understand the biology of these unique macrophages, multiple labs, including ours, have attempted to isolate these cells by flow cytometry. We demonstrated that many cells that stain positive for the macrophage marker CD169 are not macrophages, but rather correspond to a population of IL-17-committed lymphocytes that acquire macrophage-derived CD169+ membrane fragments. These IL-17-committed IL-7Ra+CCR6+ lymphocytes were present at the lymph node subcapsular sinus and migrated in close association with CD169+ SSMs. We suggest that crosstalk between SSMs and IL-17-committed lymphocytes may promote lymph node barrier immunity.

Innate-like IL-17-committed lymphocytes are an important source of IL-17 in a variety of infections and autoimmune diseases. Building on our observation that these cells, including IL-17-committed gdT cells (gdT17), are enriched in skin-draining lymph nodes, we asked whether a related gdT cell population was present in the skin and subsequently identified a population of IL-7Ra+ CCR6+ RORgt+ gdT cells resident in the mouse dermis. Intravital imaging revealed that gdT cells migrate in the dermis, while epidermal gdT cells are stationary. Dermal gdT cells rapidly produced IL-17A in vitro following exposure to IL-1b and IL-23. We suggest that dermal gdT17 cells are an important source of IL-17A during the early stages of cutaneous infection.

Finally, we made the fortuitous observation that a commonly used congenic CD45.1+ C57BL/6 mouse substrain is characterized by a selective deficiency for the Vg4+ subset of gdT17 cells. We identified a spontaneous mutation in the transcription factor Sox13 in this strain, and suggest that Sox13 is intrinsically required for the development of Vg4+ gdT17 cells. In a mouse model of psoriasis-like dermatitis, we observed a dramatic expansion of Vg4+ gdT17 cells in the draining lymph node followed by their accumulation in inflamed skin. Vg4+ gdT17 cells selectively homed to inflamed skin following transfer, suggesting that these cells may recirculate from lymph nodes to inflamed peripheral tissues. Sox13 mutant mice, which lack Vg4+ gdT17 cells, are protected from psoriasis-like changes in this model of skin disease.