Nature：niche可以保护造血干细胞免疫逃避

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一项新的研究发现骨髓造血干细胞(HSC)niche（专门作为干细胞栖身之处的小环境）是一个“有免疫特权”的地方。这个特性已知存在于睾丸、卵巢和毛囊中，但未曾被普遍性地证明存在于所有干细胞小环境中。高分辨率体内成像研究表明，调控性T细胞在HSC干细胞niche中积累，使移植的异体HSC能够逃避异体排斥。除了支持干细胞功能外，这个niche相对来说也许还提供了一个躲避免疫攻击的庇护所，这种庇护作用在某些情况下也可能会为恶性细胞所利用。* m/ y/ |- \& y: ^

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7 a9 t. _' N" u" r% Q: U  nIn vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche/ j9 y8 q# p5 X( g& M

' k7 D0 ~* g/ F! WJoji Fujisaki,1, 2 Juwell Wu,1, 2, 3 Alicia L. Carlson,1 Lev Silberstein,2, 4 Prabhakar Putheti,5 Rafael Larocca,5 Wenda Gao,5 Toshiki I. Saito,6, 9 Cristina Lo Celso,2, 4 Hitoshi Tsuyuzaki,7 Tatsuyuki Sato,7 Daniel Côté,8 Megan Sykes,6, 9 Terry B. Strom,5 David T. Scadden2, 4 & Charles P. Lin1, 2
* U+ a) A: V9 N) M: e. ~/ ~7 _Affiliations Contributions Corresponding authors Journal name: ( i9 i) b# M4 b1 T
Nature  Volume:  474,  Pages: 216–219  Date published:  (09 June 2011)  DOI:  doi:10.1038/nature10160 2 {, G" B7 ^$ ?! X
Received 19 September 2009 Accepted 27 April 2011 Published online 08 June 2011
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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.& Z+ l: e/ H* P" c* E. L0 K; r: \

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