Cocker, ATH

Imami, N

Johnson, MR

Sassine, AJ

Sivarajasingam, SP

Journal of the Society for Gynecologic Investigation

Spiral - Imperial College Digital Repository

Disrupted	Immunological	Equilibrium	of	Decidual	Natural	Killer	Cells	and	Regulatory	T	Cells	with	Onset	of	Labour		SP	Sivarajasingam1,	ATH	Cocker1,	AJ	Sassine1,	N	Imami1,	MR	Johnson1	1Imperial	College	London,	London,	United	Kingdom		Introduction:	Labour	is	recognised	as	an	inflammatory	process	and	immune	cells	particularly	at	the	maternal-fetal	interface,	 the	 decidua,	may	 hold	 the	 key	 to	 triggering	 this	 inflammation.	 The	 decidua	 consists	 of	both	 innate	 and	 adaptive	 immune	 cells,	 predominantly	 made	 up	 of	 natural	 killer	 (NK)	 cells,	monocytes	and	T	cells.	A	fine	balance	of	both	innate	and	adaptive	immunity	is	necessary	to	maintain	a	healthy	pregnancy;	hence	this	study	aims	to	 look	at	the	relationship	of	NK	cells	and	regulatory	T	cells	(Tregs)	at	term	and	at	onset	of	term	labour.		Methods:	Participants	 undergoing	 term	 non-labouring	 elective	 (TNL=8)	 and	 term	 emergency	 caesarean	sections	 in	 early	 labour	 (TeL=5;	 defined	 as	 contractions	 at	 least	 1	 every	 10	minutes	 and	 cervical	dilatation	≤3cm)	were	consented	and	recruited	from	Chelsea	and	Westminster	Hospital	labour	ward.	Lymphocytes	were	 isolated	 from	decidua	basalis,	placenta,	maternal	whole	blood	and	cord	blood;	flow	 cytometric	 analysis	 was	 performed	 to	 determine	 NK	 cell	 subsets	 (CD56/CD16)	 and	 Tregs	(CD4/CD25/CD127).	Statistical	analysis	was	undertaken	using	Prism	version	6.0	and	Stata	14.1.	Cell	population	variation	was	assessed	by	Mann	Whitney	testing.	Statistical	significance	was	defined	as	p	<0.05.	Results:	Decidual	CD56bright	NK	cells	were	significantly	raised	with	onset	of	 labour	(p=0.01)	which	was	not	mirrored	 in	 the	 other	 compartments.	 There	 was	 no	 significant	 difference	 noted	 in	 the	 cytolytic	(CD56+CD16+,	 p=0.09)	 or	 anergic	 (CD56-CD16+,	 p=0.17)	 NK	 cell	 subsets	 in	 decidua	 or	 other	compartments.	 Tregs	 maintained	 their	 frequency	 with	 onset	 of	 labour	 in	 all	 compartments.	Interestingly	 a	 regression	 analysis	 between	 Tregs	 and	 total	 NK	 cells	 in	 the	 decidua	 showed	 a	statistically	significant	 inverse	correlation	 in	TNL	(-0.19,	95%	CI	 (-0.26-	-0.12),	p<0.0001)	which	was	disrupted	 in	 TeL	 (-0.14,	 95%	 CI	 (-0.65	 –	 0.35),	 p	 =0.41).	 This	 relationship	 was	 not	 seen	 in	 the	placenta,	maternal	or	cord	blood.		Conclusion:	CD56bright	NK	 cells	may	play	 a	major	 role	 as	 effective	 cytokine	 (TNF-α,	 IFN-ƴ,	 IL-10)	producers	 in	initiating	 inflammation	 in	 the	 decidua	 and	 potentiating	 onset	 of	 labour.	 Loss	 of	 the	 equilibrium	between	NK	cells	and	Tregs	in	labouring	decidua	suggests	not	only	a	mechanism	of	communication	between	 both	 innate	 and	 adaptive	 immune	 systems	 to	 regulate	 immune	 tolerance	 and	maintain	pregnancy,	 but	 also	 highlights	 the	 extraordinary,	 and	 poorly	 understood	 role	 of	 decidual	immunology	in	human	labour.		Characters	with	spaces	2681	Max	characters	inclusive	of	title,	authors	and	institutions	-	2700		

Disrupted immunological equilibrium of decidual natural killer cells and regulatory T cells with onset of labour

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