IL33 RECEPTOR EXPRESSION IS SIGNIFICANTLY UP-REGULATED ON B CELLS DURING PREGNANCY

JURIOL LV; VENTIMIGLIA MS; MUZZIO DO; QUIROGA MF; ABBA MC; ZYGMUNT M; JENSEN F

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

IL33 is an alarmin released during cell injury caused by stress orinfection and drives immune cells into regulatory functions to main-tain tissue homeostasis.In the context of pregnancy, IL33 was recently shown to inducethe production of anti-inflammatory molecules by decidual B cells,protecting against preterm labor in human and mouse.Here we aimed to fully characterize the expression of IL33 recep-tor (IL33R) in B cells during pregnancy.We began performing a genome-wide transcriptome profiling inpure isolated B cells from the spleen of pregnant (P) and non-preg-nant C57BL/6 mice (NP). Interestingly, we observed that expressionof Il1rl1 (IL33R) was significantly upregulated (≈ 4,5 fold changes)in B cells from P compared to NP mice using Limma eBayes test(p<0.0001). This was confirmed at the protein level by flow cytom-etry. Further analysis showed that IL33R was predominantly ex-pressed on splenic B220lowCD23 low/neg B cells. A kinetic analysisdepicted that numbers of splenic B220lowCD23 low/neg IL33R + B cellswere significantly increased at early pregnancy (day 12) comparedto NP mice. At mid-pregnancy (day 14), numbers of B220 low CD23 low/negIL33R + B cells dropped as compared to day 12 but were still sig-nificantly higher than in NP mice. At late pregnancy (day 16), num-bers of B220 low CD23 low/neg IL33R + B cells were similar to NP mice(one-way ANOVA in randomized blocks, p<0.0001). Similarly, peri-toneal B1 B cells from P mice displayed significantly higher levels ofIL33R expression than NP mice (Unpaired t test p=0.0005). Next,we cultured splenocytes from NP virgin C57BL/6 females with es-tradiol (E2), progesterone (P4) or both and analyzed the expressionof IL33R on CD19 + B220 low B cells after 24h. We observed a modestincrease of IL33R expression on CD19 + B220 low B1 B cells upon E2treatment.Our results reinforce the idea of IL33 being a crucial cytokine con-trolling pregnancy outcome through a mechanism involving B cells.Keywords: Preterm labor, B cells, IL33R expression, pregnancyoutcome.