| First Author | Ghosh D | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 5 | Pages | 1783-1795 |
| PubMed ID | 28733485 | Mgi Jnum | J:250016 |
| Mgi Id | MGI:6100026 | Doi | 10.4049/jimmunol.1601972 |
| Citation | Ghosh D, et al. (2017) IL-17 Promotes Differentiation of Splenic LSK(-) Lymphoid Progenitors into B Cells following Plasmodium yoelii Infection. J Immunol 199(5):1783-1795 |
| abstractText | Lineage(-)Sca-1(+)c-Kit(-) (LSK(-)) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature B cells in response to Plasmodium yoelii infection in mice. Furthermore, LSK(-) derived B cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific Ab-secreting cells, as well as germinal center and memory B cells. However, the factors that promote their differentiation into B cells in the spleen postinfection are not defined. In this article, we show that LSK(-) cells produce the cytokine IL-17 in response to Plasmodium infection. Using Il-17ra(-/-) mice, IL-17R signaling in cells other than LSK(-) cells was found to support their differentiation into B cells. Moreover, primary splenic stromal cells grown in the presence of IL-17 enhanced the production of CXCL12, a chemokine associated with B cell development in the bone marrow, by a population of IL-17RA-expressing podoplanin(+)CD31(-) stromal cells, a profile associated with fibroblastic reticular cells. Subsequent blockade of CXCL12 in vitro reduced differentiation of LSK(-) cells into B cells, supporting a direct role for this chemokine in this process. Immunofluorescence indicated that podoplanin(+) stromal cells in the red pulp were the primary producers of CXCL12 after P. yoelii infection. Furthermore, podoplanin staining on stromal cells was more diffuse, and CXCL12 staining was dramatically reduced in Il-17ra(-/-) mice postinfection. Together, these results identify a distinct pathway that supports lymphoid development in the spleen during acute Plasmodium infection. |
