TY - JOUR
T1 - Lineage -Sca1 +c-Kit -CD25 + cells are IL-33-responsive type 2 innate cells in the mouse bone marrow
AU - Brickshawana, Adipong
AU - Shapiro, Virginia Smith
AU - Kita, Hirohito
AU - Pease, Larry R.
PY - 2011/12/1
Y1 - 2011/12/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1102242
DO - 10.4049/jimmunol.1102242
M3 - Article
C2 - 22048767
AN - SCOPUS:82755190059
SN - 0022-1767
VL - 187
SP - 5795
EP - 5804
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -