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Kupffer cell
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==Development== Development of an initial population of Kupffer cells begins in the embryonic [[yolk sac]] where [[Hematopoietic stem cell|precursor cells]] differentiate into fetal [[macrophage]]s. Once they enter the blood stream, they migrate to the [[fetal liver]] where they stay. There they complete their differentiation into Kupffer cells. Under normal conditions, these Kupffer cell populations are long-lived and self-renewing.<ref>{{cite journal | vauthors = Naito M, Hasegawa G, Takahashi K | title = Development, differentiation, and maturation of Kupffer cells | journal = Microscopy Research and Technique | volume = 39 | issue = 4 | pages = 350β64 | date = November 1997 | pmid = 9407545 | doi = 10.1002/(SICI)1097-0029(19971115)39:4<350::AID-JEMT5>3.0.CO;2-L | s2cid = 21193303 }}</ref> However, if resident Kupffer cell populations are depleted, monocytes derived from [[hematopoietic stem cell]]s in the bone marrow and transported through blood circulation to the liver can also fully differentiate into true Kupffer cells. Unlike other tissue macrophages, which must be continually renewed by circulating monocytes, these monocyte-derived Kupffer cells are capable of self-renewal once a population is established.<ref>{{cite journal | vauthors = Scott C, Zheng F, De Baetselier P, et al | title = Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells | journal = Nature Communications | volume = 7, 10321 (2016) | date = 27 January 2016 | page = 10321 | doi = 10.1038/ncomms10321 | pmid = 26813785 | pmc = 4737801 | bibcode = 2016NatCo...710321S | doi-access = free }}</ref> Development of mature Kupffer cells is regulated by numerous growth factors, with macrophage colony-stimulating factor ([[CSF1]]) playing a key role. Cytokines involved in [[type 2 inflammation]], such as [[Interleukin 4|IL-4]], may also stimulate Kupffer cell proliferation. A time frame of 14 to 21 days for complete replenishment of Kupffer cell populations has been demonstrated in animal studies. Despite high monocyte influx and maturation rates, hepatic Kupffer cell populations are tightly maintained. Evidently, there is a high rate of turnover, with the average lifespan of a Kupffer cell estimated at 3.8 days. However, the ultimate fate of Kupffer cells '' in vivo '' is not yet fully understood.<ref name=":2">{{Citation|last1=Basit|first1=Hajira|title=Histology, Kupffer Cell|date=2020|url=http://www.ncbi.nlm.nih.gov/books/NBK493226/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29630278|access-date=2020-08-25|last2=Tan|first2=Michael L.|last3=Webster|first3=Daniel R.}}</ref><ref>{{Cite journal|title=Kupffer Cells in Non-alcoholic Fatty Liver Disease: Friend or Foe?|url=https://www.ijbs.com/v16p2367.htm|access-date=2020-08-31|journal=International Journal of Biological Sciences|year=2020 |doi=10.7150/ijbs.47143 |language=en |last1=Chen |first1=Jiajia |last2=Deng |first2=Xiaoyi |last3=Liu |first3=Yongjian |last4=Tan |first4=Qiuhua |last5=Huang |first5=Guidong |last6=Che |first6=Qishi |last7=Guo |first7=Jiao |last8=Su |first8=Zhengquan |volume=16 |issue=13 |pages=2367β2378 |pmid=32760204 |pmc=7378652 }}</ref><ref name=":1" />
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