Open AccessMyelopoiesis in spleen‐producing distinct dendritic‐like cells
Author(s) -
Tan Jonathan K. H.,
O’Neill Helen C.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01490.x
Subject(s) - biology , spleen , progenitor cell , haematopoiesis , dendritic cell , myelopoiesis , stem cell , adoptive cell transfer , myeloid , stromal cell , in vivo , immunology , microbiology and biotechnology , antigen , t cell , cancer research , immune system , genetics
Dendritic cells (DC) represent a heterogeneous class of antigen presenting cells (APC). Previously we reported a distinct myeloid dendritic‐like cell present in spleen, as an in vivo counterpart to cells produced in murine spleen long‐term cultures (LTC‐DC). These cells, named ‘L‐DC’, were found to be functionally and phenotypically distinct from conventional (c)DC, plasmacytoid (p)DC and monocytes. These results suggested that spleen may represent a niche for development of L‐DC from endogenous progenitors. Adult murine spleen has now been investigated for the presence of L‐DC progenitors. Lineage‐negative (Lin) − ckit lo and Lin − ckit hi progenitor subsets were identified as candidate populations, and tested for ability to produce L‐DC; in vitro upon co‐culture with the spleen stromal line STX3, and in vivo after adoptive therapy into mice. Both subsets colonized STX3 stroma in vitro for L‐DC production, indicating that they contained either a common or two distinct progenitors for L‐DC. However, only the Lin − ckit hi subset gave progeny cells after adoptive transfer into lethally irradiated mice. In vivo development was however multilineage and not restricted to L‐DC development. Multilineage reconstitution reflects long‐term reconstituting haematopoietic stem cells (LT‐HSC), suggesting a close relationship between L‐DC progenitors and LT‐HSC. L‐DC were however produced in vivo in much higher number than monocytes/macrophages and cDC, indicating the presence of a specific L‐DC progenitor within the Lin − ckit hi subset. A model is advanced for development of L‐DC directly from haematopoietic progenitors in spleen and dependent on the spleen microenvironment.