Hideaki FujiwaraãM.D., Ph.D.
è žå 现èãä»ããè žç®¡GVHDãšã€ã³ãã©ããœãŒã ãšé¢ä¿æ§ã®è§£æ
Nature Communications
Microbial metabolite sensor GPR43 controls severity of experimental GVHD
2018 Sep 10;9(1):3674
Nature Microbiology
Host NLRP6 exacerbates graft-versus-host disease independent of gut microbial composition.
2019 May;4(5):800-812.
åçš®é è¡å¹¹çŽ°è移æ€ã¯è¡æ¶²æªæ§çŸæ£ã®å ç«åŠçæ ¹æ²»çæ³ã ããåçºåã³ç§»æ€ç察宿䞻ç ïŒGraft-versus-host disease; GVHDïŒã«äŒŽãå䜵çã移æ€åŸã®äž»æ»å ã§ãããGVHDã¯åçš®åå¿æ§T现èã«ããç®èãèèãè žç®¡ãäž»ãªæšçãšããå ç«åå¿ã§ãããã«ã«ã·ãã¥ãŒãªã³é»å®³å€ãçšãã掻æ§åT现èæå¶çæ³ã«ããGVHDäºé²æ³ãè¡ãããŠããããéçGVHDã®çºççã¯15â20ïŒ ãšæ¯èŒçé«çã§ãããT现èæå¶ã匷åããå ŽåãéçGVHDçºççã¯äœäžããåé¢è «çã®åçºåã³ãŠã€ã«ã¹/现èææçã«ããæ»äº¡çäžæãèµ·ãããäžæŠGVHDãçºçããå ŽåéçäŸã»ã©æ²»çæµææ§ã§ãããT现èãæšçãšããGVHDäºé²ã»æ²»çæ³ã¯éçã§ãããéçã»æ²»çæµæäŸã§ã¯å¿ ãè žç®¡GVHDãå«ãŸãã移æ€åã®æŸå°ç·ã倧éã®æããå€ã䜿çšãã移æ€åæ²»çã«ããè žç®¡çŽ°èé害ãä»ããdamage-associated molecular pattern ã«ããdanger signalãšè žç®¡çŽ°èãã¡ãŒãžã«äŒŽãè žå 现èãåŒãèµ·ããpathogen-associated molecular patternã«ããæåæ瀺现èã®æŽ»æ§ååã³ããã«ç¶ãT现èã®æŽ»æ§åãGVHDã®çºçæ©åºãšãããŠãããè¿å¹Žè žå 现èãšçš®ã ã®çŸæ£ã®é¢é£æ§ãææãããŠãããè žç®¡GVHDã®çºçã»éç床ãšè žå 现èã®é¢é£æ§ãå ±åãããŠããããã®æ©åºã¯äžæã§ããããã®ããæã ã¯GVHDã®æšçæãéèŠãªè žç®¡çŽ°èã®æŽ»æ§ååã³å ç«çŽ°èã«å¯Ÿããå¯å®¹æ§ãè žå 现èã«é¢é£ããæ°ããªGVHDäºé²ã»æ²»çæ³ã®ç¢ºç«ãè©Šã¿ããæ¬ç 究ã§ã¯GVHDçºçã«äŒŽãè žå 现è代è¬ç©ã§ããshort chain fatty acidãæžå°ããããšåã³ãã®è žç®¡çŽ°èã«ãããå容äœã§ããG-protein-coupled receptor 43 ïŒGPR43ïŒã®çºçŸäœäžã«äŒŽãè žç®¡ãã¡ãªã¹ã¿ã·ã¹ã®ç°åžžãèæ¯ã«ããäºãå€æãããGPR43ã¯è žç®¡çŽ°èã«é«çºçŸããŠããããã®ã·ã°ãã«ã®äœäžãã现èå Extracellular Signal-Regulated Kinase ïŒERKïŒã®ãªã³é žåäœäžåã³ã€ã³ãã©ããœãŒã ïŒç¹ã«NLRP3ïŒã®äžæŽ»åã«äŒŽãIL-1/IL-18ã®ç£çäœäžã è žç®¡çŽ°èã®æŽ»æ§åãé»å®³ãT现èã«ãã现èå·å®³ãžã®æµææ§ãæžããŠããããšãèŠåºã ããããããŸã§ã€ã³ãã©ããœãŒã ãä»ããIL-1/IL-18ã¯äž»ã«æŽ»æ§åããæåæ瀺现èã«ããç£çããGVHDã®éçåã«å¯äžãããšèããããŠããããè žç®¡çŽ°èã§ã¯çŽ°èã®æŽ»æ§åã«éèŠã§ããäºãæ¬ç 究ã§æãããšãªã£ããButyrateãpropionateã®çµå£æäžã«ããè žç®¡çŽ°èä¿è·äœçšã¯ãå®äŸ¡ã»ç°¡äŸ¿ã§ããä»åŸT现èãæåæ瀺现èãæšçãšããå ç«æå¶å€ãšç°ãªããå ç«æå¶ãåŒãèµ·ãããªãGVHDäºé²ã»æ²»çæ³ã«ãªãããå¯èœæ§ã瀺ãããçŸåšãã·ã¬ã³å€§åŠã«ãããŠåçš®é è¡å¹¹çŽ°è移æ€æ£è ã«ãããè žå 现è代è¬ç©ãä»ããGVHDäºé²ã®èšåºç 究ãè¡ãããŠããããã®çµæãæåŸ ãããã
Nature Microbiology
åçš®é è¡å¹¹çŽ°è移æ€ã¯è¡æ¶²æªæ§çŸæ£ã®æ ¹æ²»çæ³ãšããŠç¢ºç«ãããæ²»çæ³ã§ãããããããªããäŸç¶ãšããŠç§»æ€åŸã®åçºåã³ç§»æ€ç察宿䞻ç ïŒGraft-versus-host disease; GVHDïŒã«äŒŽãå䜵çã移æ€åŸã®äž»æ»å ã§ãããGVHDã¯ç§»æ€ãããåçš®åå¿æ§T现èã«ããæ¹èµ·ãããT现èãæšçãšããå ç«æå¶çæ³ç¢ºç«ãããã«ãé¢ããããéçGVHDã®çºççã¯15â20ïŒ ãšæ¯èŒçé«çã§ãããT现èæå¶ã匷åããå ŽåãéçGVHDçºççã¯äœäžããåé¢è «çã®åçºåã³ãŠã€ã«ã¹/现èææçã«ããæ»äº¡çäžæãèªããããããŸããäžæŠGVHDãçºçããå ŽåéçäŸã»ã©æ²»çæµææ§ãšã§ããããã®ãããT现èã®ã¿ãæšçãšããGVHDäºé²ã»æ²»çæ³ã¯éçã§ãããGVHDã¯äž»ã«ç®èã»èèã»è žç®¡ã«çºçããéçã»æ²»çæµæäŸã§ã¯å¿ ãè žç®¡GVHDãå«ãŸããã移æ€åæ²»çã«ããè žç®¡çŽ°èé害ïŒdamage-associated molecular patterns ã«ããdanger signalïŒãšè žç®¡çŽ°èé害ã«äŒŽãè žå 现èã«ããpathogen-associated molecular pattern ã«ããæåæ瀺现èã®æŽ»æ§ååã³ããã«ç¶ãT现èã®æŽ»æ§åãGVHDã®çºçæ©åºãšããŠèšŒæãããŠãããã€ã³ãã©ããœãŒã ã¯ãããã®ã·ã°ãã«ãæç¥ãããã®æŽ»æ§åã¯IL-1ãIL-18ãªã©ã®ççæ§ãµã€ãã«ã€ã³ã®ç£çãããã°ã©ã 现èæ»ãªã©å€çš®å€æ§ãªççå¿çãæ¹èµ·ããããã®ã·ã¹ãã ã¯å€æ¥æåã®èªèã«ãã宿䞻é²åŸ¡ã«åãããå åšååã®æ€ç¥ã§ã¯å šèº«ã§äžé©åãã€æ ¢æ§çãªççå¿çãèªå°ãå€å²ã«ãããçŸæ£ã®çºçã»å¢æªã«é¢äžãããå è¡ç 究ïŒFujiwara et al, Nat Commun, 2018ïŒã«ããGVHDã«ãããŠã€ã³ãã©ããœãŒã ã®äžã€ã§ããNLRP3ã¯æåæ瀺现èãšT现èã®æŽ»æ§åãè žç®¡äžç®çŽ°èã«ãããäžæŽ»åã«ããæåžžæ§åªå€±ã»å ç«å¯å®¹æ§äœäžãšããGVHDæªåãããããããäžæ¹ã§ãåæ§ã«IL-1/18ç£çã«é¢äžããã€ã³ãã©ããœãŒã ã§ããNLRP6ã¯è žå 现èå¢ã®åœ¢æãè žç®¡ã®æåžžæ§ç¶æã«é¢äžããŠãããèªç¶å ç«ç³»çŽ°èãšè žç®¡çŽ°èã«åºãçºçŸããã®æŽ»æ§åã¯æè žç®¡ççäœçšãèªããããŠãããæåæ瀺现èãäžå¿ãšãã宿䞻ã¯GVHDã®çºçé²å±ã«åŒ·ãå¯äžããŠããè žç®¡çŽ°èã¯GVHDã®äž»ãªæšçèåšã§ããè žç®¡ã§ãããèå³æ·±ãããšã«ãNLRP6ãä»ããè žçä¿è·äœçšãšç°ãªãNLRP6ã¯GVHDãæªåãããäºãæ¬ç 究ã«ããæãããšãªã£ãããã®äœçšã¯è žç®¡ã«ãããNLRP6ã®çºçŸã«äŸåããŠãããNLRP6ã®ã¢ãŽãã¹ãã§ããã¿ãŠãªã³ïŒèæ±é žãšçµåãè žå 现èã«ããè žç®¡ããå解åžåãããïŒãæäžã«ããGVHDãå¢æªãããä»åŸãå ç«çŽ°èãæšçãšããªãGVHDäºé²ã»æ²»çæ³ãšããŠãè žç®¡çŽ°èãæšçãšããNLRP6ã®é»å®³å€ã®å¯èœæ§ãæ¬ç 究ã§ç€ºããã
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