Lineage− Sca1+ c-Kit− CD25+ cells are IL-33–responsive Type 2 innate cells in the mouse bone marrow

A Brickshawana, VS Shapiro, H Kita… - The Journal of …, 2011 - journals.aai.org
A Brickshawana, VS Shapiro, H Kita, LR Pease
The Journal of Immunology, 2011journals.aai.org
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 …
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, ip 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.
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