{"id":35398,"date":"2020-07-07T00:12:30","date_gmt":"2020-07-06T16:12:30","guid":{"rendered":"https:\/\/case.ntu.edu.tw\/blog\/?p=35398"},"modified":"2020-07-03T15:54:03","modified_gmt":"2020-07-03T07:54:03","slug":"%e9%80%a0%e8%a1%80%e5%b9%b9%e7%b4%b0%e8%83%9e%e5%85%b7%e5%85%8d%e7%96%ab%e8%a8%98%e6%86%b6%ef%bc%8c%e7%82%bacovid-19%e7%96%ab%e8%8b%97%e9%96%8b%e7%99%bc%e9%8b%aa%e8%b7%af%ef%bc%9f","status":"publish","type":"post","link":"https:\/\/case.ntu.edu.tw\/blog\/?p=35398","title":{"rendered":"\u9020\u8840\u5e79\u7d30\u80de\u5177\u514d\u75ab\u8a18\u61b6\uff0c\u70baCOVID-19\u75ab\u82d7\u958b\u767c\u92ea\u8def\uff1f"},"content":{"rendered":"

\u9020\u8840\u5e79\u7d30\u80de\u53ef\u4ee5\u5206\u5316\u51fa\u5404\u7a2e\u8840\u7403\uff0c\u5c0d\u4eba\u9ad4\u517c\u5177\u4fdd\u8b77\u548c\u6cbb\u7642\u7684\u529f\u80fd\u3002\u6700\u8fd1\u7684\u7814\u7a76\u986f\u793a\u7d93\u904e\u6559\u80b2\u7684\u9020\u8840\u5e79\u7d30\u80de\u53ef\u7522\u751f\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\uff0c\u9084\u6709\u514d\u75ab\u8a18\u61b6\u7684\u80fd\u529b\uff0c\u800c\u4e14\u9019\u7a2e\u514d\u75ab\u8a18\u61b6\u5177\u6709\u5ee3\u6cdb\u7684\u4fdd\u8b77\u4f5c\u7528\uff0c\u4e26\u4e0d\u9650\u65bc\u6700\u521d\u63a5\u89f8\u7684\u75c5\u539f\u9ad4\u3002\u6b64\u5916\uff0c\u53ef\u8a98\u5c0e\u5148\u5929\u6027\u514d\u75ab\u8a18\u61b6\u7684\u5361\u4ecb\u82d7\u4e5f\u4f5c\u7528\u65bc\u9020\u8840\u5e79\u7d30\u80de\uff0c\u9019\u7a2e\u75ab\u82d7\u4e5f\u6b63\u5728\u9032\u884c\u7814\u7a76\u4ee5\u6e2c\u8a66\u5176\u5c0dCOVID-19\u7684\u6709\u6548\u6027\u53ca\u5b89\u5168\u6027\u3002\u56e0\u6b64\uff0c\u9019\u4e9b\u7814\u7a76\u6210\u679c\u61c9\u6709\u52a9\u65bcCOVID-19\u75ab\u82d7\u7684\u958b\u767c\u3002<\/strong><\/span><\/p>\n

\u6587\uff0f\u9673\u6df5\u9293<\/strong><\/p>\n

\u25cf\u9020\u8840\u5e79\u7d30\u80de\u7684\u8a8d\u8b58<\/strong><\/span><\/p>\n

\u9020\u8840\u5e79\u7d30\u80de\uff08hematopoietic stem cell, HSC\uff09\u53ef\u4ee5\u5206\u5316\u51fa\u8840\u6db2\u7d30\u80de\u8207\u514d\u75ab\u7d30\u80de\uff0c\u5982\u904b\u8f38\u6c27\u6c23\u7684\u7d05\u8840\u7403\u3001\u62b5\u6297\u611f\u67d3\u7684\u767d\u8840\u7403\u3001\u5e6b\u52a9\u51dd\u8840\u7684\u8840\u5c0f\u677f\u53ca\u7522\u751f\u6297\u9ad4\u7684\u6dcb\u5df4\u7403\u7b49\u3002HSC\u5177\u6709\u591a\u6f5b\u80fd\u6027\uff08multipotency\uff09\u548c\u81ea\u6211\u66f4\u65b0\uff08self-renewal\uff09\u7684\u7279\u6027\uff0c\u5206\u5316\u51fa\u7684\u8840\u7403\u53ef\u4ee5\u5206\u6210\u9aa8\u9ad3\u7fa4\u7cfb\uff08myeloid lineage\uff09\u548c\u6dcb\u5df4\u7fa4\u7cfb\uff08lymphoid lineage\uff09\u5169\u7a2e\uff0c\u524d\u8005\u5305\u542b\u55ae\u6838\u7403\u3001\u5de8\u566c\u7d30\u80de\u3001\u55dc\u4e2d\u6027\u767d\u8840\u7403\u3001\u55dc\u9e7c\u6027\u767d\u8840\u7403\u3001\u55dc\u9178\u6027\u767d\u8840\u7403\u3001\u80a5\u5927\u7d30\u80de\uff08mast cell\uff09\u3001\u7d05\u8840\u7403\u53ca\u8840\u5c0f\u677f\uff1b\u5f8c\u8005\u5247\u6709\u81ea\u7136\u6bba\u624b\u7d30\u80de\u3001\u6bba\u624b\u7d30\u80de\u3001T\u7d30\u80de\u3001B\u7d30\u80de\u53ca\u6f3f\u7d30\u80de\uff08[plasma cell\uff09\u7b49\u3002HSC\u5df2\u77e5\u53ef\u7528\u4f86\u6cbb\u7642\u8a31\u591a\u8840\u6db2\u3001\u816b\u7624\u3001\u5148\u5929\u4ee3\u8b1d\u7570\u5e38\u53ca\u514d\u75ab\u7f3a\u9677\u7b49\u75be\u75c5\u3002\u6b64\u5916\uff0c\u6cbb\u7642\u764c\u75c7\u4f7f\u7528\u7684\u6297\u764c\u85e5\u7269\u3001\u5316\u5b78\u6cbb\u7642\u6216\u653e\u5c04\u7dda\u7642\u6cd5\u96d6\u53ef\u6bba\u6b7b\u764c\u7d30\u80de\uff0c\u4f46\u4e5f\u6642\u5e38\u50b7\u5bb3\u5230\u5065\u5eb7\u7684HSC\uff0c\u5982\u679c\u79fb\u690d\u65b0\u7684HSC\u7d66\u75c5\u4eba\uff0c\u53ef\u88fd\u9020\u51fa\u65b0\u7684\u8840\u6db2\u8207\u514d\u75ab\u7d30\u80de\u800c\u5ef6\u7e8c\u60a3\u8005\u751f\u547d\u3002<\/p>\n

\"\"
\u5716\u7247\u4f86\u6e90: pixabay<\/figcaption><\/figure>\n

\u25cfC\/EBP\u03b2<\/strong>\u4f9d\u8cf4\u6027\u7684\u8868\u89c0\u907a\u50b3\u8a18\u61b6\u53ef\u5728<\/strong>HSC<\/strong>\u4e2d\u8a98\u767c\u8a13\u7df4\u514d\u75ab\u4f5c\u7528<\/strong><\/span><\/p>\n

\u57282020\u5e74\uff0c\u6cd5\u570b\u570b\u5bb6\u5065\u5eb7\u8207\u91ab\u5b78\u7814\u7a76\u9662\u3001\u570b\u5bb6\u79d1\u5b78\u7814\u7a76\u4e2d\u5fc3\u53ca\u5fb7\u570b\u5fb7\u52d2\u65af\u767b\u518d\u751f\u6cbb\u7642\u4e2d\u5fc3\u7684\u7814\u7a76\u4eba\u54e1\u767c\u73feHSC\u4e0d\u50c5\u80fd\u88fd\u9020\u65b0\u7684\u8840\u6db2\u7d30\u80de\u548c\u514d\u75ab\u7d30\u80de\uff0c\u9084\u5177\u6709\u300c\u514d\u75ab\u8a18\u61b6 (immune memory) \u300d\u7684\u80fd\u529b\uff0c\u80fd\u8ffd\u8e64\u904e\u53bb\u88ab\u7d30\u83cc\u6216\u75c5\u6bd2\u611f\u67d3\u7684\u60c5\u6cc1\uff0c\u4ee5\u4fbf\u5c07\u4f86\u53ef\u4ee5\u5f15\u767c\u66f4\u5feb\u53ca\u66f4\u6709\u6548\u7684\u514d\u75ab\u53cd\u61c9\uff0c\u76f8\u95dc\u7814\u7a76\u7d50\u679c\u5df2\u520a\u767b\u65bc\u570b\u969b\u671f\u520a\u300aCell Stem Cell\u300b\uff0c\u5167\u5bb9\u7684\u91cd\u9ede\u6709\u56db\uff1a(1)\u9810\u5148\u66b4\u9732\u904e\u8102\u591a\u91a3\uff08lipopolysaccharide, LPS\uff09\u7684HSC\u53ef\u4fdd\u6709\u5148\u524d\u611f\u67d3\u6311\u6230\uff08previous infectious challenge\uff09\u7684\u8868\u89c0\u907a\u50b3\u8a18\u61b6\uff08epigenetic memory\uff09\uff1b(2)\u958b\u653e\u6027\u9aa8\u9ad3\u589e\u5f37\u5b50\uff08myeloid enhancer\uff09\u53ef\u4fc3\u9032\u4e8c\u6b21\u523a\u6fc0\uff08secondary stimulation\uff09\u7684\u8f49\u9304\u53cd\u61c9\uff1b(3)\u514d\u75ab\u8a18\u61b6\u53ef\u6539\u5584\u9aa8\u9ad3\u5206\u5316\u548c\u5c0d\u4e8c\u6b21\u611f\u67d3\uff08secondary infection\uff09\u7684\u62b5\u6297\u529b\uff1b(4) LPS\u8a98\u5c0e\u7684\u514d\u75ab\u8a18\u61b6\u7522\u751f\u9700\u8981\u5148\u5c0e\u8f49\u9304\u56e0\u5b50\uff08pioneer transcription factor\uff09\uff0dC\/EBP\u03b2\u7684\u8f14\u52a9\u3002<\/p>\n

\u5df2\u77e5\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\uff08innate immunity\uff09\u80fd\u5c0d\u611f\u67d3\u7522\u751f\u5373\u6642\u4fdd\u8b77\uff0c\u4e26\u5177\u6709\u67d0\u7a2e\u5f62\u5f0f\u7684\u8a18\u61b6\uff0c\u4f46\u8a73\u7d30\u7684\u6a5f\u5236\u4ecd\u4e0d\u6e05\u695a\uff0c\u6240\u4ee5\u9019\u500b\u7814\u7a76\u5718\u968a\u63a8\u6e2c\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\u7684\u8a18\u61b6\u53ef\u80fd\u662f\u5728HSC\u4e2d\u5f62\u6210\u7684\u3002\u4ed6\u5011\u70ba\u9a57\u8b49\u6b64\u5047\u8a2d\uff0c\u9996\u5148\u5c07\u53d6\u81ea\u5927\u8178\u687f\u83cc\u8868\u9762LPS\u6ce8\u5c04\u5230\u514d\u75ab\u52dd\u4efb\uff08immunocompetent\uff09\u5c0f\u9f20\u9ad4\u5167\uff0c\u518d\u5c07\u5f9e\u9019\u4e9b\u5c0f\u9f20\u8eab\u4e0a\u7372\u5f97\u7684HSC\u8f49\u6b96\u5230\u672a\u53d7\u7d30\u83cc\u611f\u67d3\u7684\u514d\u75ab\u529f\u80fd\u4f4e\u4e0b\u7684\uff08immunocompromised\uff09\u5c0f\u9f20\u9ad4\u5167\uff0c\u5229\u7528\u9019\u4e9bHSC\u91cd\u5efa\u514d\u75ab\u529f\u80fd\u4f4e\u4e0b\u5c0f\u9f20\u7684\u514d\u75ab\u7cfb\u7d71\uff0c\u63a5\u8457\u5728\u52d5\u7269\u6311\u6230\u6e2c\u8a66\uff08animal challenge test\uff09\u6642\u4f7f\u7528\u7da0\u81bf\u687f\u83cc\uff08Pseudomonas aeruginosa<\/em>\uff09\u611f\u67d3\u9019\u7d44\u5c0f\u9f20\uff0c\u7d50\u679c\u986f\u793a\u9019\u4e9b\u5c0f\u9f20\u7684\u6b7b\u4ea1\u7387\u50c5\u70ba25\uff05\uff0c\u4f46\u662f\u672a\u6ce8\u5c04HSC\u7684\u5c0d\u7167\u7d44\u5c0f\u9f20\u7684\u6b7b\u4ea1\u7387\u5247\u9ad8\u905475\uff05\u3002<\/p>\n

\u4ed6\u5011\u66f4\u9032\u4e00\u6b65\u767c\u73feLPS\u8a98\u5c0e\u7684\u514d\u75ab\u8a18\u61b6\u9700\u8981C\/EBP\u03b2\u7684\u8f14\u52a9\u624d\u80fd\u9032\u884c\uff0c\u5df2\u77e5\u9aa8\u9ad3\u589e\u5f37\u5b50\u5bcc\u542bC\/EBP\u03b2\u6a19\u9776\uff0c\u800cC\/EBP\u03b2 \u7f3a\u5931\u6703\u6d88\u9664LPS\u8a98\u5c0e\u7684\u8868\u89c0\u907a\u50b3\u6a19\u8a18\uff08epigenetic mark\uff09\u548c\u57fa\u56e0\u8868\u73fe\u7684\u9577\u671f\u5370\u8a18\uff08long-term inscription\uff09\u3002\u56e0\u6b64\uff0c\u5728\u4e8c\u6b21\u611f\u67d3\u671f\u9593\uff0c\u77ed\u671f\u514d\u75ab\u8a0a\u606f\u50b3\u905e\u80fd\u8a98\u5c0eC\/EBP\u03b2\u4f9d\u8cf4\u6027\u7684\u67d3\u8272\u8cea\u53ef\u7372\u5f97\u6027\uff08chromatin accessibility\uff09\uff0c\u9032\u800c\u8a98\u5c0eHSC\u7684\u8a13\u7df4\u514d\u75ab\u4f5c\u7528\uff08trained immunity\uff09\uff0c\u9810\u5148\u66b4\u9732\u904e LPS\u7684HSC\u8868\u73fe\u66f4\u6709\u6548\u7387\u7684\u9aa8\u9ad3\u589e\u5f37\u5b50\u53cd\u61c9\uff0c\u4ee5\u589e\u52a0\u9aa8\u96a8\u7684\u5206\u5316\u3001\u986f\u73fe\u8f03\u4f73\u7684\u7d30\u83cc\u6e05\u9664\u7387\u548c\u5c0f\u9f20\u5b58\u6d3b\u7387\uff0c\u9019\u5efa\u7acb\u4e86\u4e00\u7a2e\u6a5f\u5236\u4f86\u6558\u660e\u611f\u67d3\u6b77\u53f2\uff08infection history\uff09\u5982\u4f55\u5728HSC\u88ab\u8868\u89c0\u907a\u50b3\u5316\u800c\u4fc3\u6210\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\u7684\u6574\u9ad4\u8a18\u61b6\u529f\u80fd\u3002\u6b64\u5916\uff0c\u4ed6\u5011\u767c\u73fe\u8a72\u6a5f\u5236\u4e26\u4e0d\u9650\u65bc\u7279\u5b9a\u7684\u75c5\u539f\u9ad4\uff0c\u56e0\u70ba\u5728\u53e6\u4e00\u500b\u5be6\u9a57\u4e2d\uff0c\u5148\u524d\u66b4\u9732\u65bc\u75c5\u6bd2\u6297\u539f\u7684HSC\uff0c\u4ea6\u80fd\u4fdd\u8b77\u5c0f\u9f20\u514d\u65bc\u53d7\u5230\u7da0\u81bf\u687f\u83cc\u7684\u4e8c\u6b21\u611f\u67d3\u3002\u7d50\u679c\u986f\u793aHSC\u5177\u6709\u514d\u75ab\u8a18\u61b6\u80fd\u529b\uff0c\u82e5\u5c07\u63a5\u89f8\u904e\u75c5\u539f\u9ad4\u7684HSC\u79fb\u690d\u5230\u5c0f\u9f20\u5167\uff0c\u4fbf\u80fd\u589e\u5f37\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\uff0c\u800c\u4e14\u9019\u7a2e\u514d\u75ab\u8a18\u61b6\u4e0d\u6703\u4fb7\u9650\u65bc\u6700\u521d\u9047\u5230\u7684\u75c5\u539f\u9ad4\uff0c\u53ef\u7522\u751f\u5ee3\u6cdb\u7684\u514d\u75ab\u4fdd\u8b77\u4f5c\u7528\u3002<\/p>\n

\u25cf\u5361\u4ecb\u82d7\u6559\u80b2<\/strong>HSC<\/strong>\u7522\u751f\u4fdd\u8b77\u6027\u7684\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\u4ee5\u5c0d\u6297\u80ba\u7d50\u6838<\/strong><\/span><\/p>\n

\u57282018\u5e74\uff0c\u52a0\u62ff\u5927\u7814\u7a76\u4eba\u54e1\u8b49\u660e\u6559\u80b2HSC\u53ef\u4ee5\u8a98\u767c\u8a13\u7df4\u514d\u75ab\u4f5c\u7528\u3002\u4ed6\u5011\u767c\u73fe\u80ba\u7d50\u6838\u75ab\u82d7\uff0d\u5361\u4ecb\u82d7\uff08Bacillus Calmette\u2013Gue\u00b4rin, BCG\uff09\u9032\u5165\u9aa8\u9ad3\u5f8c\u53ef\u6539\u8b8aHSC\u548c\u591a\u529f\u80fd\u524d\u9a45\u7d30\u80de\uff08multipotent progenitor\uff09\u7684\u8f49\u9304\u4f5c\u7528\uff0c\u5c0e\u81f4\u5c40\u90e8\u7d30\u80de\u64f4\u589e\u548c\u9aa8\u9ad3\u751f\u6210\u4f5c\u7528\u589e\u5f37\u3002\u6b64\u5916\uff0cBCG\u53ef\u8a13\u7df4HSC\u7522\u751f\u8868\u89c0\u907a\u50b3\u4fee\u98fe\u904e\u7684\u5de8\u566c\u7d30\u80de\uff0c\u8207\u539f\u4f86\u7684\u5de8\u566c\u7d30\u80de\u76f8\u6bd4\uff0c\u9019\u7a2e\u7d30\u80de\u66f4\u80fd\u63d0\u4f9b\u8f03\u597d\u7684\u4fdd\u8b77\u4ee5\u62b5\u6297\u7d50\u6838\u687f\u83cc\uff08Mycobacterium tuberculosis<\/em>\uff09\u3002\u4ed6\u5011\u4f7f\u7528\u751f\u7269\u5171\u751f\u548c\u5d4c\u5408\u5c0f\u9f20\uff08parabiotic and chimeric mice\uff09\u53ca\u904e\u7e7c\u8f49\u79fb\uff08adoptive transfer\uff09\u65b9\u6cd5\uff0c\u8b49\u660e\u85c9\u7531BCG\u8a98\u5c0e\u7684HSC\u91cd\u65b0\u7de8\u7a0b\uff08reprogramming\uff09\u4ee5\u8a13\u7df4\u55ae\u6838\u7d30\u80de\/\u5de8\u566c\u7d30\u80de\u7684\u4f5c\u7528\u5728\u6d3b\u9ad4\u5167\u662f\u53ef\u6301\u7e8c\u7684\uff0c\u8b49\u660e\u91dd\u5c0dHSC\u8259\u5ba4\uff08compartment\uff09\u7684\u6a19\u9776\u4f5c\u7528\uff08targeting\uff09\u53ef\u63d0\u4f9b\u65b0\u7684\u75ab\u82d7\u958b\u767c\u65b9\u6cd5\u3002<\/p>\n

\u25cf\u7d50\u8ad6<\/strong><\/span><\/p>\n

HSC\u7d93\u904e\u6559\u80b2\u8a13\u7df4\u5f8c\u5177\u6709\u6f5b\u529b\u8a98\u767c\u5148\u5929\u6027\u514d\u75ab\u4f5c\u7528\uff0c\u4e26\u5177\u6709\u514d\u75ab\u8a18\u61b6\u80fd\u529b\uff0c\u53ef\u63d0\u4f9b\u4e00\u5b9a\u7a0b\u5ea6\u7684\u4fdd\u8b77\u4ee5\u62b5\u6297\u7d30\u83cc\u7684\u611f\u67d3\uff0c\u76ee\u524d\u4e5f\u6b63\u5728\u9032\u884c\u76f8\u95dc\u7814\u7a76\u4ee5\u6e2c\u8a66\u5176\u5c0d\u65b0\u51a0\u80ba\u708e\uff08COVID-19\uff09\u75ab\u82d7\u7684\u5f71\u97ff\u3002\u4e0a\u8ff0\u7814\u7a76\u7d50\u679c\u4e0d\u50c5\u589e\u52a0\u4eba\u5011\u5c0d\u514d\u75ab\u7cfb\u7d71\u548cHSC\u529f\u80fd\u7684\u7406\u89e3\uff0c\u9084\u6709\u52a9\u65bc\u63a8\u52d5\u75ab\u82d7\u7684\u7814\u767c\uff0c\u7279\u5225\u662f\u5728COVID-19\u4ecd\u8513\u5ef6\u5168\u7403\u7684\u60c5\u5f62\u4e0b\uff0c\u61c9\u6df1\u5177\u6f5b\u529b\u5354\u52a9\u958b\u767c\u65e2\u5b89\u5168\u53c8\u6709\u6548\u7684\u75ab\u82d7\u3002<\/p>\n

\u53c3\u8003\u8cc7\u6599\uff1a<\/strong><\/p>\n

    \n
  1. de Laval B, Maurizio J, Kandalla PK, Brisou G, Simonnet L, Huber C, Gimenez G, Matcovitch-Natan O, Reinhardt S, David E, Mildner A, Leutz A, Nadel B, Bordi C, Amit I, Sarrazin S, Sieweke MH. CEBP\u03b2-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells. Cell Stem Cell. 2020 May 7;26(5):657-674.e8. doi: 10.1016\/j.stem.2020.01.017. Epub 2020 Mar 12.<\/li>\n
  2. Kaufmann E, Sanz J, Dunn JL, Khan N, Mendon\u00e7a LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-L\u00e9onard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M. BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity Against Tuberculosis. Cell. 2018 Jan 11;172(1-2):176-190.e19. doi: 10.1016\/j.cell.2017.12.031.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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