title: Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow.
abstract: IL-33 promotes type 2 immune responses, both protective and pathogenic. Recently, targets of IL-33, including several newly discovered type 2 innate cells, have been characterized in the periphery. In this study, we report that bone marrow cells from wild-type C57BL/6 mice responded with IL-5 and IL-13 production when cultured with IL-33. IL-33 cultures of bone marrow cells from Rag1 KO and Kit(W-sh/W-sh) mice also responded similarly; hence, eliminating the possible contributions of T, B, and mast cells. Rather, intracellular staining revealed that the IL-5- and IL-13-positive cells display a marker profile consistent with the Lineage(-)Sca-1(+)c-Kit(-)CD25(+) (LSK(-)CD25(+)) cells, a bone marrow cell population of previously unknown function. Freshly isolated LSK(-)CD25(+) cells uniformly express ST2, the IL-33 receptor. In addition, culture of sorted LSK(-)CD25(+) cells showed that they indeed produce IL-5 and IL-13 when cultured with IL-33 plus IL-2 and IL-33 plus IL-7. Furthermore, i.p. injections of IL-33 or IL-25 into mice induced LSK(-)CD25(+) cells to expand, in both size and frequency, and to upregulate ST2 and α(4)β(7) integrin, a mucosal homing marker. Thus, we identify the enigmatic bone marrow LSK(-)CD25(+) cells as IL-33 responsive, both in vitro and in vivo, with attributes similar to other type 2 innate cells described in peripheral tissues.
authors: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors: Adipong
authors: A
authors: Brickshawana
authors: Virginia Smith
authors: VS
authors: Shapiro
authors: Hirohito
authors: H
authors: Kita
authors: Larry R
authors: LR
authors: Pease
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; C508018:Il2ra protein, mouse; C506535:Il33 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000067596:Interleukin-33; D007378:Interleukins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit