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RESEARCH PRODUCT

Transplanting the genetic susceptibility to Crohn’s disease

subject

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Susceptibility to Crohn’s disease may be transferred via haematopoietic stem cells, highlighting the pivotal role of genetic factors in the pathogenesis of Crohn’s disease Crohn’s disease (CD) is one of the two most common forms of inflammatory bowel disease (IBD). The prevalence of CD has increased in Western countries over the past decades and mainly young patients are affected, with a peak incidence between 15 and 35 years.1 The aetiology of IBD is still unclear and should be considered as multifactorial according to recent studies.2 Genetic factors seem to play a pathogenic role as well as environmental, infectious, and immunological factors. All of these different aetiological aspects are reconciled in a paradigm, in which CD could result from disturbances of the intestinal barrier and pathological activation of the intestinal immune response towards luminal bacterial antigens in individuals with genetic susceptibility. Immunological key players for the pathogenesis of CD have been identified, including cellular components such as lamina propria macrophages and CD4+ T lymphocytes as well as cytokines such as tumour necrosis factor α (TNF-α), interleukin (IL)-6, IL-12, IL-18, and others.1–3 Identification of these pathogenetically relevant factors has been greatly facilitated by the availability of appropriate animal models, in particular genetically engineered knockout mice or transgenic mice, respectively. When SCID mice lacking functional B cells and T cells are reconstituted with a special subset of CD4+ T helper cells expressing the surface markers CD45Rbhigh or CD62L, they develop chronic colitis.4 These T helper cell subsets are thought to differentiate preferentially towards Th1 cells in the host producing those proinflammatory cytokines that are involved in the pathogenesis of CD, such as TNF-α.5,6 To date, however, clinical and experimental evidence for the role of distinct mononuclear cell populations has been limited. There are some reports on …