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In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche


Stem cells reside in a specialized regulatory microenvironment or niche1,2, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity1,2,3. The niche may also protect stem cells from environmental insults3 including cytotoxic chemotherapy and perhaps pathogenic immunity4. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression4. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche1,2,5,6,7 in the bone marrow, a site where immune reactivity exists8,9. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (Treg) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with Treg cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. Treg cells seem to participate in creating a localized zone where HSPCs reside and where Treg cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.

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Figure 1: Allo-HSPCs survive without immunosuppression for 30 days.
Figure 2: FoxP3 T reg cells accumulate on the endosteal surface, form clusters around adoptively transferred HSPCs and around allo-HSPCs that survive after 30 days.
Figure 3: Bone marrow T reg cells are critical in suppressing the rejection of allo-HSPCs in immune-competent recipients in an IL-10-dependent manner.


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This work was supported by Bullock fellowship (to J.F.), the Harvard Stem Cell Institute and DoD W81XWH-10-1-0217 (to J.F. and C.P.L.), NIH HL097748 (to C.P.L.), HL97794 (to D.T.S.), CA111519 (to M.S.), AI041521 (to T.B.S), EMBO (to C.L.C.), HFSP (to C.L.C.), philanthropic sources (to D.T.S. and C.L.C.), and the National Institutes of Health. We acknowledge J. Zhao and D. Cao for cell sorting.

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Authors and Affiliations



J.F. conceived the overall project, designed and performed experiments, analysed data and wrote the manuscript. J.W. and A.L.C. contributed to intravital imaging. L.S. and J.F. performed histology analysis. P.P. and J.F. performed qRT–PCR analysis. R.L. and J.F. performed FACS analysis using intracellular staining. W.G. performed mouse breeding. J.F., H.T. and T.S. performed HSPC isolation. D.C. generated software for IVM. T.I.S., C.L.C., M.S., T.B.S. and D.T.S. provided advice on the design of experiments. D.T.S. edited the manuscript. C.P.L. helped design experiments, supervised the overall study and wrote the manuscript.

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Correspondence to Joji Fujisaki or Charles P. Lin.

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The authors declare no competing financial interests.

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Fujisaki, J., Wu, J., Carlson, A. et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature 474, 216–219 (2011).

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