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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

Type 1 lymphocyte (IL18R1+) and Type 2 lymphocyte (IL1RL1+) percentage.(A) The values are shown as percentage of Type 1 lymphocyte subsets in control (Ctr) and T1DM patients during pregnancy and postpartum. None of the Type 1 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) differ significantly across pregnancy or postpartum. (B) Percentage of Type 2 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) from control (Ctr) and T1DM patients during pregnancy and postpartum. Type 2 CD56bright NK cells (*P<0.05), CD56dim NK cells and T cells were significantly augmented in the 2nd trimester compared to 1st trimester from control, but not from T1DM patients. Differences also were detected in Type 2 CD56bright NK cells between 2nd and 3rd trimester from control patients (*P<0.05); Comparison between control and T1DM patients demonstrated that at postpartum, differences were observed in the Type 2 CD56bright NK cells (*P<0.05).
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pone.0119526.g003: Type 1 lymphocyte (IL18R1+) and Type 2 lymphocyte (IL1RL1+) percentage.(A) The values are shown as percentage of Type 1 lymphocyte subsets in control (Ctr) and T1DM patients during pregnancy and postpartum. None of the Type 1 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) differ significantly across pregnancy or postpartum. (B) Percentage of Type 2 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) from control (Ctr) and T1DM patients during pregnancy and postpartum. Type 2 CD56bright NK cells (*P<0.05), CD56dim NK cells and T cells were significantly augmented in the 2nd trimester compared to 1st trimester from control, but not from T1DM patients. Differences also were detected in Type 2 CD56bright NK cells between 2nd and 3rd trimester from control patients (*P<0.05); Comparison between control and T1DM patients demonstrated that at postpartum, differences were observed in the Type 2 CD56bright NK cells (*P<0.05).

Mentions: The proportions of lymphocyte subsets (CD56bright NK, CD56dim NK, NKT and T cells) expressing IL18R1 (Type 1 cells) did not differ significantly between control and T1DM patients over pregnancy and postpartum (Fig. 3A; S3 Table). However, Type 2 (IL1RL1+) CD56bright NK, CD56dim NK and T cells increased significantly in control patients in 2nd trimester (Fig. 3B; S3 Table; P<0.05), while lymphocytes from T1DM patients expressing IL1RL1 were invariant over pregnancy and postpartum (Fig. 3B; S3 Table). NKT cells were invariant across pregnancy and postpartum in control and T1DM patients. These data suggest that specific subsets of CD56bright NK, CD56dim NK and T cells participate in the shift of immunity from Type 1 towards Type 2 in 2nd trimester of normal pregnancy. They further indicate that by 18–20 weeks gestation in T1DM patients, a physiological change fails to occur amongst CD56bright NK, CD56dim NK and T cells.


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)

Type 1 lymphocyte (IL18R1+) and Type 2 lymphocyte (IL1RL1+) percentage.(A) The values are shown as percentage of Type 1 lymphocyte subsets in control (Ctr) and T1DM patients during pregnancy and postpartum. None of the Type 1 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) differ significantly across pregnancy or postpartum. (B) Percentage of Type 2 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) from control (Ctr) and T1DM patients during pregnancy and postpartum. Type 2 CD56bright NK cells (*P<0.05), CD56dim NK cells and T cells were significantly augmented in the 2nd trimester compared to 1st trimester from control, but not from T1DM patients. Differences also were detected in Type 2 CD56bright NK cells between 2nd and 3rd trimester from control patients (*P<0.05); Comparison between control and T1DM patients demonstrated that at postpartum, differences were observed in the Type 2 CD56bright NK cells (*P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119526.g003: Type 1 lymphocyte (IL18R1+) and Type 2 lymphocyte (IL1RL1+) percentage.(A) The values are shown as percentage of Type 1 lymphocyte subsets in control (Ctr) and T1DM patients during pregnancy and postpartum. None of the Type 1 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) differ significantly across pregnancy or postpartum. (B) Percentage of Type 2 lymphocyte subsets (CD56bright NK cells, CD56dim NK cells, NKT cells and T cells) from control (Ctr) and T1DM patients during pregnancy and postpartum. Type 2 CD56bright NK cells (*P<0.05), CD56dim NK cells and T cells were significantly augmented in the 2nd trimester compared to 1st trimester from control, but not from T1DM patients. Differences also were detected in Type 2 CD56bright NK cells between 2nd and 3rd trimester from control patients (*P<0.05); Comparison between control and T1DM patients demonstrated that at postpartum, differences were observed in the Type 2 CD56bright NK cells (*P<0.05).
Mentions: The proportions of lymphocyte subsets (CD56bright NK, CD56dim NK, NKT and T cells) expressing IL18R1 (Type 1 cells) did not differ significantly between control and T1DM patients over pregnancy and postpartum (Fig. 3A; S3 Table). However, Type 2 (IL1RL1+) CD56bright NK, CD56dim NK and T cells increased significantly in control patients in 2nd trimester (Fig. 3B; S3 Table; P<0.05), while lymphocytes from T1DM patients expressing IL1RL1 were invariant over pregnancy and postpartum (Fig. 3B; S3 Table). NKT cells were invariant across pregnancy and postpartum in control and T1DM patients. These data suggest that specific subsets of CD56bright NK, CD56dim NK and T cells participate in the shift of immunity from Type 1 towards Type 2 in 2nd trimester of normal pregnancy. They further indicate that by 18–20 weeks gestation in T1DM patients, a physiological change fails to occur amongst CD56bright NK, CD56dim NK and T cells.

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