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 4β 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.
ASJC Scopus subject areas
- Immunology and Allergy