免疫病の分子・遺伝子治療に関する研究

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Representative results which have been obtained by the studies done between 1993-1996 under the support by the Grant-in-Aid for Specially Promoted Research are as follows ;i) Outline of the signal transduction through IL-6 receptor and gp130 has been elucidated, i.e.two signalling pathways have been identified, namely a) JAK-STAT3/APRF pathway and b) Ras-Map kinase cascade and activation of NF-IL6.ii) Targetted disruption of the genes inyolved in the cytokine signalling revealed the hitherto unknown in vivo function of the signalling molecules such as gp130, STAT3, STAT6 and NF-IL6. NF-IL6 knockout mice were completely sensitive to Listeria infection, revealing the essential role of NF-IL6 in bactericidal activity of macrophage. gp130 knockout was lethal and cardiac muscle development was impared, revealing the essential role of the signals through gp130 for cardiac muscle development and prevention of apoptosis.iii) A chemokine (PBSF/SDF-1) and its receptor which are one of the essential factor for pre B cell development, have been cloned and the results have revealed that a receptor for PBSF/SDF-1 functions as a HIV coreceptor, fusin.iv) The genes encoding coreceptors for B lymphocyte activation, CD40 and CD23 have been knocked out and in vivo roles of these molecules in humoral and T cell-dependent cellular immunity are revealed.v) Experimental treatments of patients with multiple myeloma, Castleman's disease and rheumatoid arthritis with humanized anti-IL6 receptor antibody have been carried out and its effectiveness on these diseases are confirmed.