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...