The major goal of the laboratory is to understand the function of the innate immune system, particularly in host-pathogen recognition and disease pathophysiology. We discovered physiological function of NOD2, the strongest genetic factor of Crohn’s disease. We established an animal model for NOD2-dependent, Th1-dominant granulomatous ileitis, which is useful for drug development for Crohn’s disease because of its striking similarity to the human disease. We found that another NLR family member, NLRC5/CITA, is a transcriptional regulator of MHC class I molecules and related genes. Although CIITA has been known as a master regulator of MHC class II genes for the last two decades, a counterpart regulator of MHC class I genes had not been identified. This discovery advanced our understanding on MHC or human HLA genes, which are important in infectious disease, cancer and transplanted medicine.
Innate Immunity, Toll-like receptor, NLR protein, Crohn’s disease, MHC gene regulation
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Meissner TB, Li A, Biswas A, Lee KH, Liu YJ, Bayir E. Iliopoulos D, van den Elsen PJ, Kobayashi KS. (2010). NLR family member NLRC5 is a transcriptional regulator of MHC class I genes. Proc Natl Acad Sci USA. 107 (31): 13794-9.
Biswas A, Liu YJ, Hao L, Mizoguchi A. Salzman NH, Bevins CL, Kobayashi KS. (2010). Induction and rescue of Nod2-dependent Th1-driven granulomatous inflamemation of the ileum. Proc Natl Acad Sci USA. 107(33):14739-44.
Meissner, T.B., Liu, Y-J., Lee, K-H., Li A., Biswas, A., van Eggermond, M.C.J.A., van den Elsen, P., Kobayashi, K.S. (2012) NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression. J Immunol, 188(10):4951-8.
Biswas, A., Meissner, T.B., Kawai, T., Kobayashi, K.S. (2012) Impaired MHC Class I Expression in Mice Deficient for Nlrc5/CITA. J Immunol, 189(2):516-20
Lee, K-H., Biswas, A., Liu, Y-J., Kobayashi, K.S. (2012) Proteasomal degradation of Nod2 mediates tolerance to bacterial cell wall components. J. Biol Chem, 287(47):39800-11.
Kobayashi, K.S. and van den Elsen, P. (2012) NLRC5/MHC class I transactivator: a key regulator of class I mediated immune responses. Nat Rev Immunol, 12(12):813-20.