Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

Katakai, Tomoya; Suto, Hidenori; Sugai, Manabu; Gonda, Hiroyuki; Togawa, Atsushi; Suematsu, Sachiko; Ebisuno, Yukihiko; Katagiri, Koko; Kinashi, Tatsuo; Shimizu, Akira

doi:10.4049/jimmunol.181.9.6189

Cited by 214 publications

(298 citation statements)

References 58 publications

(73 reference statements)

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“…Moreover, upon inflammation or immune response, there is a dramatic increase in the LN stromal compartment, which raises the question about the origin and plasticity of LN resident stromal cells. While local proliferation has been suggested [55], circulating stromal cell precursors, such as MSCs, have been proposed to contribute to stromal compartment expansion [54,56,57]. Our data strongly support that ASCs are recruited during the establishment of an immune response.…”

Section: Discussionsupporting

confidence: 76%

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

et al. 2013

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Adipose tissue (AT) has become accepted as a source of multipotent progenitor cells, the adipose stromal cells (ASCs). In this regard, considerable work has been performed to harvest and characterize this cell population as well as to investigate the mechanisms by which transplanted ASCs mediate tissue regeneration. In contrast the endogenous release of native ASCs by AT has been poorly investigated. In this work, we show that native ASCs egress from murine AT. Indeed, we demonstrated that the release of native ASCs from AT can be evidenced both using an ex vivo perfusion model that we set up and in vivo. Such a mobilization process is controlled by CXCR4 chemokine receptor. In addition, once mobilized from AT, circulating ASCs were found to navigate through lymph fluid and to home into lymph nodes (LN). Therefore, we demonstrated that, during the LN activation, the fat depot encapsulating the activated LN releases native ASCs, which in turn invade the activated LN. Moreover, the ASCs invading the LN were visualized in close physical interaction with podoplanin and ER-TR7 positive structures corresponding to the stromal network composing the LN. This dynamic was impaired with CXCR4 neutralizing antibody. Taken together, these data provide robust evidences that native ASCs can traffic in vivo and that AT might provide stromal cells to activated LNs. STEM CELLS

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Section: Discussionsupporting

confidence: 76%

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

et al. 2013

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“…1D). Co-localisation of CD248 and gp38 was observed only within the capsule in close proximity to the region where marginal reticular cells have been described [14]. Therefore, these data suggest CD248 is associated with an as yet undefined stromal cell whose occurrence coincides with the initial response of pLN to NP-CGG.…”

Section: Cd248 Expression Is Associated With Initial Pln Expansionmentioning

confidence: 56%

“…All experiments were performed in accordance with UK laws with approval of local ethics committees. Frozen sections of tissues were prepared and stained by immunohistochemistry as described previously [14]. …”

mentioning

confidence: 99%

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

et al. 2010

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CD248 is a cell surface receptor that specifically identifies fibroblasts and pericytes during development and in association with cancer and inflammation. However, its function is poorly defined and its role in lymphoid organs not studied. Here, we used (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation and mice lacking CD248 to study whether CD248 modulates popliteal LN (pLN) expansion and subsequent immune responses. We have found that CD248 is required for complete pLN expansion but not for co-ordination of B and T cell compartmentalisation or antibody production following (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation. In vitro, we show that CD248 expression in human MG63 stromal cells and mouse embryonic fibroblasts leads to a pro-proliferative and pro-migratory phenotype. This correlates with a proliferating CD248 1 population observed in vivo during pLN expansion. Taken together, these data highlight a role for CD248 in secondary lymphoid organ remodelling during adaptive immune responses.Key words: CD248 . Endosialin . Fibroblast . Lymphoid tissue . Stromal cells IntroductionDuring an immune response, secondary lymphoid organs (SLO) expand significantly. However, mechanisms that regulate this have been relatively understudied with leucocyte accumulation rather than stromal cell expansion being the focus. Logic dictates that there has to be co-ordinated expansion of tissue structure to accommodate the rapidly expanding leucocyte populations. This expansion includes not only an intricate network of fibroblasts that provide an important structural scaffold but also the formation of new blood and lymph vessels to oxygenate and allow transport of lymphocytes into and out of the organ [1].CD248/endosialin is a relatively new marker for a subset of stromal cells in developing tissues. It is a member of an emerging transmembrane protein family implicated in tissue remodelling and repair, which includes CD141 and CD93 [2,3] 1884expressed on fibroblasts and pericytes during development and in tumour-associated stroma [4][5][6][7]. An important role for CD248 within tumour stroma has been highlighted in CD248-deficient mice; abdominal tumours implanted into mice lacking CD248 demonstrated reduced growth, invasion and metastasis [8]. This, coupled with the finding that CD248 expression is regulated by hypoxia inducible factor-2a [9], suggests that CD248 may provide an important link between hypoxia and tissue remodelling allowing synchronisation of these processes.We have previously proposed a role for CD248 in development and infection-dependent activation of SLO stroma [10]. Whether CD248 is required for tissue remodelling was not explored nor was its function. Therefore, to more fully understand the requirements for CD248 during remodelling, we compared the degree of popliteal LN (pLN) expansion in WT and CD248 KO mice following immunisation with (4-hydroxy-3-nitrophenyl)acetyl chicken g-globulin (NP-CGG). The ability of CD248 to regulate cell migration and proliferation in vitro w...

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“…Growth of developing CPs relies on the continued cross talk between LTi cells, which express RANK, RANKL and CXCR5, and VCAM-1 ϩ organizer cells that express RANKL and CXCL13 upon LT␤R signaling. 34,35 Decreased LT␣ 1 ␤ 2 expression caused by absence of RANKL may lead to loss of CXCL13 expression, which in turn inhibits further CP development and prevents their maturation into ILFs.…”

Section: Discussionmentioning

confidence: 99%

Distinct Developmental Requirements for Isolated Lymphoid Follicle Formation in the Small and Large Intestine

Knoop

Butler

Kumar

et al. 2011

The American Journal of Pathology

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Cryptopatches (CPs) and isolated lymphoid follicles (ILFs) are organized intestinal lymphoid tissues that develop postnatally in mice and include stromal cells expressing the receptor activator of nuclear factor kappa-B ligand (RANKL). We investigated how stromal RANKL influences the development and differentiation of CPs and ILFs by analyzing the development of these lymphoid structures in knockout mice lacking RANKL. We found that RANKL ؊/؊ mice had a fourfold reduction in the overall density of CPs in the small intestine compared to control mice, with the largest decrease in the proximal small intestine. No B cells were present in CPs from the small intestine of RANKL ؊/؊ mice and ILF formation was completely blocked. In sharp contrast, colonic ILFs containing B cells were present in RANKL ؊/؊ mice. Stromal cells within CPs in the small intestine of RANKL ؊/؊ mice did not express CXCL13 (originally called B lymphocyte chemoattractant) and often lacked other normally expressed stromal cell antigens, whereas colonic lymphoid aggregates in RANKL ؊/؊ mice retained stromal CXCL13 expression. The CXCL13-dependent maturation of precursor CPs into ILFs is differentially regulated in the small intestine and colon, with an absolute requirement for RANKL only in the small intestine.

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Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs

Cited by 214 publications

References 58 publications

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

Distinct Developmental Requirements for Isolated Lymphoid Follicle Formation in the Small and Large Intestine

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