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Discovery of highly immunogenic spleen-resident FCGR3+CD103+ cDC1s differentiated by IL-33-primed ST2+ basophils" ÀÔ´Ï´Ù.
IL-33Àº IL-1 family¿¡ ¼ÓÇÏ´Â nuclear cytokineÀÌÀÚ alarminÀ¸·Î¼ type II immune cellÀÎ basophil, Th2 cell, eosinophils, mast cell, ILC2 µîÀ» ÀÚ±ØÇÏ¿© infection, inflammatory disease, cancer¿Í °°Àº »óȲ¿¡¼ Áß¿äÇÑ Á¶Àý ÀÛ¿ëÀ» ÇÏ´Â ºÐÀÚ·Î ¾Ë·ÁÁ® ÀÖ½À´Ï´Ù.
ƯÈ÷ Tumor »óȲ¿¡¼ IL-33ÀÇ ¿ªÇÒÀº ¾ÆÁ÷±îÁö Á¤È®ÇÏ°Ô ¹àÇôÁ® ÀÖÁö ¾ÊÀ¸¸ç, Treg cell expansionÀ» À¯µµÇÏ¿© tumor-promoting pathway¸¦ À¯µµÇϰųª, tumor-associated macrophageÀÇ mobilizationÀ» ÅëÇØ tumor growth¸¦ À¯µµÇÑ´Ù´Â ¿¬±¸ °á°úµéÀÌ Á¸ÀçÇÏ¿´½À´Ï´Ù.
±×·¯³ª ÀÌ¿Í´Â ¹Ý´ë·Î, ¸î¸î ¿¬±¸µéÀº IL-33°¡ antitumor immunity¸¦ À¯µµÇÏ´Â cytokineÀ¸·Î¼, eosinophil activationÀ» À¯µµÇϰųª, tumor-residing dendritic cellÀ» maturation½ÃÄÑ antitumor T-cell response¸¦ À¯µµÇÏ´Â µî Ç×¾Ï Ä¡·áÁ¦ÀÇ adjuvant·Î¼ÀÇ °¡´É¼ºÀ» Á¦½ÃÇϱ⵵ ÇÏ¿´½À´Ï´Ù.
ÇÏÁö¸¸ ¾ÆÁ÷±îÁö IL-33°¡ ¸Å°³ÇÏ´Â antitumor immune response¿¡ ´ëÇÑ ÀÚ¼¼ÇÑ immunological mechanismÀÌ ¹àÇôÁ® ÀÖÁö ¾Ê¾Ò±â ¶§¹®¿¡, ÇØ´ç ¿¬±¸ÁøÀº recombinant IL-33¸¦ tumor-bearing (TB) mice¿¡ ó¸®ÇÑ ÈÄ tumor growthÀÇ ¾î¶°ÇÑ ¿µÇâÀ» ¹ÌÄ¡´Â Áö Á¶»çÇÏ¿´½À´Ï´Ù.
±× °á°ú·Î IL-33¸¦ ó¸®ÇÑ TB mouse ±×·ì¿¡¼ Tumor growth°¡ °¨¼ÒÇÏ´Â °ÍÀ» È®ÀÎÇÏ¿´°í, ÀÌ·¯ÇÑ È¿°ú°¡ conventional DC°¡ ¾ø´Â Batf3 KO mice¿¡¼´Â ³ªÅ¸³ªÁö ¾Ê´Â °Í ¶ÇÇÑ È®ÀÎÇÏ¿´½À´Ï´Ù.
ÀÌ¿¡ IL-33 treated mouse¿Í Control mouse¸¦ ºñ±³ÇßÀ» ¶§ spleen ³»¿¡¼ CD103+ cDC1 ±ºÁýÀÌ Áõ°¡ÇÏ´Â °ÍÀ» È®ÀÎÇÏ¿´À¸¸ç, ÇØ´ç ±ºÁýÀÇ T-cell priming ability ¶ÇÇÑ °ÈµÇ¾î ÀÖÀ½À» È®ÀÎÇÏ¿´½À´Ï´Ù.
¶ÇÇÑ IL-33 treatment »óȲ¿¡¼ ºÐȽÃŲ DC¿¡¼ FCGR3ÀÇ ¹ßÇöÀÌ Áõ°¡ÇÏ¿´À¸¸ç OVA-immune complex uptake ¹× OT-I T cell priming ability°¡ Áõ°¡ÇÑ °ÍÀ» È®ÀÎÇÏ¿´½À´Ï´Ù.
Ãß°¡ÀûÀ¸·Î IL-33°¡ CD103+ DC development¿¡ ¾î¶°ÇÑ ¿µÇâÀ» ¹ÌÃÆ´ÂÁö È®ÀÎÇϱâ À§ÇØ ST2 (IL-33 receptor) KO mouse strainÀ» È°¿ëÇÏ¿© in vitro DC development¸¦ È®ÀÎÇßÀ» ¶§, ST2 KO mouse¿¡¼ À¯·¡ÇÑ splenocyte¿¡¼µµ CD103+ DC°¡ ºÐÈÇÏ´Â °ÍÀ» È®ÀÎÇÏ¿© IL-33°¡ DC development¿¡ extrinsicÇÏ°Ô ¿µÇâÀ» ¹ÌÄ¡´Â °ÍÀ» È®ÀÎÇß½À´Ï´Ù.
ÀÌ·¯ÇÑ Çö»óÀº ST2¸¦ ¹ßÇöÇÏ°í ÀÖ´Â basophilÀÌ IL-33 treatment »óȲ¿¡¼ ºÐºñÇÏ´Â GM-CSF, IL-13, IL-9, IL-5 µîÀÇ extrinsic soluble factor¿¡ ÀÇÇØ ¹ß»ýÇÏ´Â °ÍÀ» È®ÀÎÇÏ¿´½À´Ï´Ù.
ÃÖÁ¾ÀûÀ¸·Î mouse tumor model¿¡¼ DC-based vaccine ¶Ç´Â human PBMC¿¡¼ moDC¸¦ ºÐȽÃÅ°´Â °úÁ¤¿¡ IL-33¸¦ ó¸®ÇÏ¿© ±× È¿°ú¸¦ È®ÀÎÇÏ¿´½À´Ï´Ù.
Áï, ÀÌ ³í¹®Àº recombinant IL-33 ¶Ç´Â IL-33-mediated DC vaccineÀÌ tumor immunotherapy¸¦ À§ÇÑ È¿°úÀûÀÎ ¼ö´ÜÀ¸·Î È°¿ëµÉ ¼ö ÀÖ´Â °¡´É¼ºÀ» Á¦½ÃÇÑ ³í¹®ÀÔ´Ï´Ù.
À§ ³í¹®Àº DC-based vaccineÀ» È°¿ëÇÑ tumor immunotherapy¿Í immunogenic dendritic cell ºÐÈ¿¡ ¿µÇâÀ» ¹ÌÄ¡´Â ÀÎÀڵ鿡 ´ëÇؼ °øºÎÇϱâ À§Çؼ ¼±Á¤ÇÏ°Ô µÇ¾ú½À´Ï´Ù.
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https://www.nature.com/articles/s41423-023-01035-8