Macrophage-regulatory T cell interactions promote type 2 immune homeostasis through Resistin-like molecule α

RELMα is a small, secreted protein expressed by T helper type 2 (Th2) cytokine activated “M2” macrophages in helminth infection and allergy. At steady state and in response to Th2 cytokines, RELMα is highly expressed by peritoneal macrophages. We generated RELMα TdTomato (Td) reporter/knockout (RΕLMαTd/Td) mice. RELMαTd/Td mice had increased IL-4 induced peritoneal macrophage responses and splenomegaly compared to RELMα+/+ mice. Nanostring data indicated that RELMαTd/Td peritoneal macrophages were more proliferative and activated than RELMα+/+ macrophages, with increased genes associated with T cell response, growth factor and cytokine signaling, but decreased genes associated with differentiation and maintenance of myeloid cells.This studies identify a new RELMα regulatory pathway whereby RELMα-expressing macrophages directly sustain Treg proliferation to limit Th2 inflammatory responses. 11 samples are included, 2 from PBS injected Rα+/+, 2 from PBS injected RαΤd/Td, 3 from IL4c injected Rα+/+ and 4 from IL4c injected RαTd/Td. Mice injected i.p. with mouse IL-4c or PBS (vehicle control) on days 0 and 2 and peritoneal cells were recovered at day 4. Peritoneal macrophages (CD11b+F4/80+) were sorted with the MoFlo Astrios cell sorter then anaylzed with Nanostring.