{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:34:25Z","timestamp":1767850465817,"version":"3.49.0"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,3,11]],"date-time":"2008-03-11T00:00:00Z","timestamp":1205193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p><jats:bold>Problem\u2002<\/jats:bold> An important subset of implantation defects\/early abortion seems to be linked with a deregulation of the interleukin (IL)\u201012\/IL\u201015\/IL\u201018 system as well as tumor necrosis factor (TNF)\u2010 and natural killer (NK)\u2010controlled\/mediated networks at the decidual placental interface, both in case of deficient or excess expression. The presence of TNF in high amounts in the pre\/peri\u2010implantation uterus and its pivotal role during pregnancy are difficult to reconcile with its abortive effects in ongoing pregnancy. We therefore searched for regulators of the IL\u201012\/IL\u201018 family of cytokines as well as for antagonist(s) of TNF with potentially selective effects on implantation.<\/jats:p><jats:p><jats:bold>Method of study\u2002<\/jats:bold> We first used Swiss mice to verify the presence in the murine reproductive tract of \u2018new members\u2019 of the IL\u201012 family of cytokines, IL\u201023 and IL\u201027, as well as of tumor necrosis factor\u2010like WEAK inducer of apoptosis (TWEAK), described as acting with TNF as Yin and Yang of innate immunity in murine placenta\/ decidua at days 0\u201312.5. We then compared expression by RT\u2010PCR in the CBA\u2003\u00d7\u2003DBA\/2, and CBA\u2003\u00d7\u2003BALB\/c murine mating combinations. Finally, we performed <jats:italic>in vivo<\/jats:italic> neutralization experiments of TWEAK and IL\u201027.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Immunohistochemistry (IHC) studies showed that IL\u201023, IL\u201027, and TWEAK were expressed at the interface. For RT\u2010PCR, IL\u201023 expression peaked at day 9.5 in the non\u2010aborting mating combination, a peak absent in the aborting one, and thus difficult to explain except by invoking a feed back on EB13 (Epstein\u2013Barr virus\u2010induced gene 3 cytokine). Most important, an immediate post\u2010mating IL\u201027 hyper expression was seen in the CBA\u2003\u00d7\u2003DBA\/2 mating compared to CBA\u2003\u00d7\u2003BALB\/c one. The difference in expression resurged and was statistically very significant by days 6.5\u20139.5, compatible with an early activation of inflammation on day 0.5 which would then peak again in the \u2018resorption window\u2019 where takes place the early NK\/mph activation described by Baines et\u00a0al. A significant TWEAK expression was present in both strains from days 0.5 to 4.5 peaking in both cases in the first days when it is known that intra uterine TNF also reaches high levels as a component of post\u2010mating inflammation. However, it was lower from day 1.5 in the abortion\u2010prone CBA\u2003\u00d7\u2003DBA\/2 mating combination, and almost absent by days 6.5\u20139.5 when compared to the non\u2010aborting CBA\u2003\u00d7\u2003BALB\/c mating combination. In both mating combinations, neutralization of TWEAK\u2010enhanced resorption rates, but surprisingly so did IL\u201027 neutralization.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> TWEAK is likely offering protection against the deleterious effects of TNF in implantation explaining embryo survival in a TNF\u2010rich environment, and equal number of implants in both strains. However, there is a clear difference of protection in abortion\u2010prone mating peaking in the abortion\/resorption window but starting early, and therefore possible links with the prevention of abortion in CBA\u2003\u00d7\u2003DBA\/2 matings by interfering with complement activation as recently described by Girardi et\u00a0al. are discussed, as well as consequences for our current view of feto\u2010maternal \u2018seed and soil\u2019 interplay. The apparently paradoxical effects of IL\u201027 neutralization are also discussed.<\/jats:p>","DOI":"10.1111\/j.1600-0897.2007.00567.x","type":"journal-article","created":{"date-parts":[[2008,3,11]],"date-time":"2008-03-11T12:37:03Z","timestamp":1205239023000},"page":"323-338","source":"Crossref","is-referenced-by-count":34,"title":["ORIGINAL ARTICLE: Immune Regulation at the Interface During Early Steps of Murine Implantation: Involvement of Two New Cytokines of the IL\u201012 Family (IL\u201023 and IL\u201027) and of TWEAK"],"prefix":"10.1111","volume":"59","author":[{"given":"Anne Elisabeth","family":"Mas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Petitbarat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Dubanchet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Fay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Led\u00e9e","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e9rard","family":"Chaouat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,3,11]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000074300"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5230-0"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)61781-6"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)62011-1"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1317"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod53.4.814"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(01)00035-2"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1997.tb00257.x"},{"key":"e_1_2_5_10_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4049\/jimmunol.143.1.9","article-title":"Murine trophoblast can be killed by lymphokine\u2010activated killer cells","volume":"143","author":"Drake BL","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1990.tb00675.x"},{"key":"e_1_2_5_12_2","volume-title":"Placental Infiltration of Resorbing CBA\u2003\u00d7\u2003DBA\/2 Embryos. 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