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Homing receptor expression is deviated on CD56+ blood lymphocytes during pregnancy in Type 1 diabetic women.

Burke SD, Seaward AV, Ramshaw H, Smith GN, Virani S, Croy BA, Lima PD - PLoS ONE (2015)

Bottom Line: The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM.Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56bright NK cells.This implicates CD56bright NK cells in diabetic pregnancy complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

ABSTRACT
Type 1 Diabetes Mellitus (T1DM) is characterized by an augmented pro-inflammatory immune state. This contributes to the increased risk for gestational complications observed in T1DM mothers. In normal pregnancies, critical immunological changes occur, including the massive recruitment of lymphocytes, particularly CD56bright NK cells, into early decidua basalis and a 2nd trimester shift towards Type 2 immunity. Decidual CD56bright NK cells arise at least partly from circulating progenitors expressing adhesion molecules SELL and ITGA4 and the chemokine receptors CXCR3 and CXCR4. In vitro studies show that T1DM reduces interactions between blood CD56+ NK cells and decidual endothelial cells by reducing SELL and ITGA4-based interactions. To address the mechanisms by which specific lymphocyte subsets may be recruited from the circulation during pregnancy and whether these mechanisms are altered in T1DM, flow cytometry was used to examine eight peripheral blood lymphocyte subsets (Type 1 (IL18R1+) and Type 2 (IL1RL1+) CD56bright NK, CD56dim NK, NKT and T cells) from control and T1DM women. Blood was collected serially over pregnancy and postpartum, and lymphocytes were compared for expression of homing receptors SELL, ITGA4, CXCR3, and CXCR4. The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM. CD56bright NK cells from control women had the highest expression of all four receptors with greatest expression in 2nd trimester. At this time, these receptors were expressed at very low levels by CD56bright NK cells from TIDM patients. Type 1/Type 2 NKT cell ratios were not influenced by either pregnancy or TIDM. Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56bright NK cells. This implicates CD56bright NK cells in diabetic pregnancy complications.

No MeSH data available.


Related in: MedlinePlus

Homing receptor expression by Type 2 CD56dim NK cells.Percentage of Type 2 CD56dim NK cells expressing SELL (A) and CXCR3 (B). (A) Type 2 CD56dim NK cells expressing SELL from control patients in 3rd trimester were higher than in 1st trimester (*P<0.05). No differences in Type 2 CD56dim NK cells were detected over pregnancy in T1DM patients. (B) Control 3rd trimester patients had a higher percentage of Type 2 CD56dim NK cells expressing CXC3 than in 1st (**P<0.01) or 2nd trimesters (*P<0.05). The Type 2 CD56dim NK cells from T1DM patients did not differ across pregnancy. Type 2 CD56dim NK cells expressing CXCR3 in the 3rd trimester were numerous in control than T1DM patients (#P<0.05).
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pone.0119526.g006: Homing receptor expression by Type 2 CD56dim NK cells.Percentage of Type 2 CD56dim NK cells expressing SELL (A) and CXCR3 (B). (A) Type 2 CD56dim NK cells expressing SELL from control patients in 3rd trimester were higher than in 1st trimester (*P<0.05). No differences in Type 2 CD56dim NK cells were detected over pregnancy in T1DM patients. (B) Control 3rd trimester patients had a higher percentage of Type 2 CD56dim NK cells expressing CXC3 than in 1st (**P<0.01) or 2nd trimesters (*P<0.05). The Type 2 CD56dim NK cells from T1DM patients did not differ across pregnancy. Type 2 CD56dim NK cells expressing CXCR3 in the 3rd trimester were numerous in control than T1DM patients (#P<0.05).

Mentions: Changes in homing receptor expression also occurred in Type 2 CD56dim NK cells. In control patients, CD56dim NK cells expressing SELL and CXCR3 were significantly higher in 3rd than in 1st or 2nd trimesters (Fig. 6A, B), while in T1DM patients no changes were detected. Type 2 CD56dim NK cells expressing CXCR3 were significant lower in T1DM than control patients at 3rd trimester (Fig. 6B).


Homing receptor expression is deviated on CD56+ blood lymphocytes during pregnancy in Type 1 diabetic women.

Burke SD, Seaward AV, Ramshaw H, Smith GN, Virani S, Croy BA, Lima PD - PLoS ONE (2015)

Homing receptor expression by Type 2 CD56dim NK cells.Percentage of Type 2 CD56dim NK cells expressing SELL (A) and CXCR3 (B). (A) Type 2 CD56dim NK cells expressing SELL from control patients in 3rd trimester were higher than in 1st trimester (*P<0.05). No differences in Type 2 CD56dim NK cells were detected over pregnancy in T1DM patients. (B) Control 3rd trimester patients had a higher percentage of Type 2 CD56dim NK cells expressing CXC3 than in 1st (**P<0.01) or 2nd trimesters (*P<0.05). The Type 2 CD56dim NK cells from T1DM patients did not differ across pregnancy. Type 2 CD56dim NK cells expressing CXCR3 in the 3rd trimester were numerous in control than T1DM patients (#P<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368780&req=5

pone.0119526.g006: Homing receptor expression by Type 2 CD56dim NK cells.Percentage of Type 2 CD56dim NK cells expressing SELL (A) and CXCR3 (B). (A) Type 2 CD56dim NK cells expressing SELL from control patients in 3rd trimester were higher than in 1st trimester (*P<0.05). No differences in Type 2 CD56dim NK cells were detected over pregnancy in T1DM patients. (B) Control 3rd trimester patients had a higher percentage of Type 2 CD56dim NK cells expressing CXC3 than in 1st (**P<0.01) or 2nd trimesters (*P<0.05). The Type 2 CD56dim NK cells from T1DM patients did not differ across pregnancy. Type 2 CD56dim NK cells expressing CXCR3 in the 3rd trimester were numerous in control than T1DM patients (#P<0.05).
Mentions: Changes in homing receptor expression also occurred in Type 2 CD56dim NK cells. In control patients, CD56dim NK cells expressing SELL and CXCR3 were significantly higher in 3rd than in 1st or 2nd trimesters (Fig. 6A, B), while in T1DM patients no changes were detected. Type 2 CD56dim NK cells expressing CXCR3 were significant lower in T1DM than control patients at 3rd trimester (Fig. 6B).

Bottom Line: The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM.Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56bright NK cells.This implicates CD56bright NK cells in diabetic pregnancy complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

ABSTRACT
Type 1 Diabetes Mellitus (T1DM) is characterized by an augmented pro-inflammatory immune state. This contributes to the increased risk for gestational complications observed in T1DM mothers. In normal pregnancies, critical immunological changes occur, including the massive recruitment of lymphocytes, particularly CD56bright NK cells, into early decidua basalis and a 2nd trimester shift towards Type 2 immunity. Decidual CD56bright NK cells arise at least partly from circulating progenitors expressing adhesion molecules SELL and ITGA4 and the chemokine receptors CXCR3 and CXCR4. In vitro studies show that T1DM reduces interactions between blood CD56+ NK cells and decidual endothelial cells by reducing SELL and ITGA4-based interactions. To address the mechanisms by which specific lymphocyte subsets may be recruited from the circulation during pregnancy and whether these mechanisms are altered in T1DM, flow cytometry was used to examine eight peripheral blood lymphocyte subsets (Type 1 (IL18R1+) and Type 2 (IL1RL1+) CD56bright NK, CD56dim NK, NKT and T cells) from control and T1DM women. Blood was collected serially over pregnancy and postpartum, and lymphocytes were compared for expression of homing receptors SELL, ITGA4, CXCR3, and CXCR4. The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM. CD56bright NK cells from control women had the highest expression of all four receptors with greatest expression in 2nd trimester. At this time, these receptors were expressed at very low levels by CD56bright NK cells from TIDM patients. Type 1/Type 2 NKT cell ratios were not influenced by either pregnancy or TIDM. Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56bright NK cells. This implicates CD56bright NK cells in diabetic pregnancy complications.

No MeSH data available.


Related in: MedlinePlus