Murine models of Omenn syndrome
J. Clin. Invest. Serre-Yu Wong, et al. 117:1213 doi:10.1172/JCI32214 [Go to this article.]

Figure 1
Schematic for the development of immunodeficiency and allergy/autoimmunity in OS. (A) Normally, V(D)J recombination is competent to produce a diverse repertoire of TCR molecules. In the thymus, normal selection processes are intact, and in the periphery, unimpeded lymphocyte development and handling of antigenic stimulation result in an immunocompetent individual. (B) In OS, genetic defects result in a restricted TCR repertoire and lymphopenia. A disrupted thymic environment, directly or indirectly caused by genetic defects, contributes to the loss of central tolerance. In the periphery, lymphopenia and IL-7 receptor (IL-7R) deficiency result in prolonged or abnormal homeostatic proliferation, which may result in Th2 skewing and loss of peripheral tolerance. In this issue of the JCI, Khiong et al. (15) implicate homeostatically proliferating T cells as a cause of Th2 skewing in a mutant mouse model of OS. Also in this issue, Marella et al. (13) show that in a mutant mouse model of OS, there is a decreased proportion of Foxp3⁺ Tregs in peripheral lymphoid organs. Other factors, including genetic, epigenetic, environmental, and iatrogenic factors, may influence disease development at any or all stages. The involvement of a severely restricted B cell repertoire remains unexplained in OS and is not depicted here.