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Composition, Development, and Function of Uterine Innate Lymphoid Cells.

Doisne JM, Balmas E, Boulenouar S, Gaynor LM, Kieckbusch J, Gardner L, Hawkes DA, Barbara CF, Sharkey AM, Brady HJ, Brosens JJ, Moffett A, Colucci F - J. Immunol. (2015)

Bottom Line: In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology.Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR(+) and partially overlap with previously described IL-22-producing uterine NK cells.This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Cambridge School of Clinical Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0SW, United Kingdom; jmd83@medschl.cam.ac.uk.

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Cytokine production by uILCs. (A) Intracellular IFN-γ in cNK cells from the spleen and in uILC1 from V, M, and D was measured upon stimulation ex vivo with either PMA and ionomycin or IL-12 and IL-15. Left panel shows data for gated uILC1s. Right panels show percentages of IFN-γ+ cells in stimulated (S) or unstimulated (NS) uILC1s (n = 3–6 experiments, mean ± SEM, unpaired t test). (B) Intracellular IL-5 and IL-13 in cells from V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-25 and IL-33. Top panels show data for gated uILC2s. Bottom panels show percentages of IL-5+ cells and IL-13+ cells among S and NS uILC2s (n = 2–6 experiments, mean ± SEM, paired t test). (C) Intracellular IL-17A and IL-22 in cells from peripheral lymph nodes (pLN); V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-1β and IL-23. Left panels show data for gated uILC3s. Right panels show percentages of IL-17A+ cells and IL-22+ cells among S and NS uILC3s (n = 2–6 experiments, mean ± SEM, paired t test). *p ≤ 0.05, **p < 0.01, ****p < 0.0001.
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fig05: Cytokine production by uILCs. (A) Intracellular IFN-γ in cNK cells from the spleen and in uILC1 from V, M, and D was measured upon stimulation ex vivo with either PMA and ionomycin or IL-12 and IL-15. Left panel shows data for gated uILC1s. Right panels show percentages of IFN-γ+ cells in stimulated (S) or unstimulated (NS) uILC1s (n = 3–6 experiments, mean ± SEM, unpaired t test). (B) Intracellular IL-5 and IL-13 in cells from V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-25 and IL-33. Top panels show data for gated uILC2s. Bottom panels show percentages of IL-5+ cells and IL-13+ cells among S and NS uILC2s (n = 2–6 experiments, mean ± SEM, paired t test). (C) Intracellular IL-17A and IL-22 in cells from peripheral lymph nodes (pLN); V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-1β and IL-23. Left panels show data for gated uILC3s. Right panels show percentages of IL-17A+ cells and IL-22+ cells among S and NS uILC3s (n = 2–6 experiments, mean ± SEM, paired t test). *p ≤ 0.05, **p < 0.01, ****p < 0.0001.

Mentions: uILC1s produced IFN-γ upon short stimulation in vitro with either PMA and ionomycin or with IL-12 and IL-15 (Fig. 5A). Compared with splenic cNK cells, fewer uILC1s produced IFN-γ, although the frequency of IFN-γ+ upon stimulation increased at midgestation (Fig. 5A).


Composition, Development, and Function of Uterine Innate Lymphoid Cells.

Doisne JM, Balmas E, Boulenouar S, Gaynor LM, Kieckbusch J, Gardner L, Hawkes DA, Barbara CF, Sharkey AM, Brady HJ, Brosens JJ, Moffett A, Colucci F - J. Immunol. (2015)

Cytokine production by uILCs. (A) Intracellular IFN-γ in cNK cells from the spleen and in uILC1 from V, M, and D was measured upon stimulation ex vivo with either PMA and ionomycin or IL-12 and IL-15. Left panel shows data for gated uILC1s. Right panels show percentages of IFN-γ+ cells in stimulated (S) or unstimulated (NS) uILC1s (n = 3–6 experiments, mean ± SEM, unpaired t test). (B) Intracellular IL-5 and IL-13 in cells from V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-25 and IL-33. Top panels show data for gated uILC2s. Bottom panels show percentages of IL-5+ cells and IL-13+ cells among S and NS uILC2s (n = 2–6 experiments, mean ± SEM, paired t test). (C) Intracellular IL-17A and IL-22 in cells from peripheral lymph nodes (pLN); V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-1β and IL-23. Left panels show data for gated uILC3s. Right panels show percentages of IL-17A+ cells and IL-22+ cells among S and NS uILC3s (n = 2–6 experiments, mean ± SEM, paired t test). *p ≤ 0.05, **p < 0.01, ****p < 0.0001.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4592103&req=5

fig05: Cytokine production by uILCs. (A) Intracellular IFN-γ in cNK cells from the spleen and in uILC1 from V, M, and D was measured upon stimulation ex vivo with either PMA and ionomycin or IL-12 and IL-15. Left panel shows data for gated uILC1s. Right panels show percentages of IFN-γ+ cells in stimulated (S) or unstimulated (NS) uILC1s (n = 3–6 experiments, mean ± SEM, unpaired t test). (B) Intracellular IL-5 and IL-13 in cells from V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-25 and IL-33. Top panels show data for gated uILC2s. Bottom panels show percentages of IL-5+ cells and IL-13+ cells among S and NS uILC2s (n = 2–6 experiments, mean ± SEM, paired t test). (C) Intracellular IL-17A and IL-22 in cells from peripheral lymph nodes (pLN); V and M were measured upon stimulation ex vivo with either PMA and ionomycin or IL-1β and IL-23. Left panels show data for gated uILC3s. Right panels show percentages of IL-17A+ cells and IL-22+ cells among S and NS uILC3s (n = 2–6 experiments, mean ± SEM, paired t test). *p ≤ 0.05, **p < 0.01, ****p < 0.0001.
Mentions: uILC1s produced IFN-γ upon short stimulation in vitro with either PMA and ionomycin or with IL-12 and IL-15 (Fig. 5A). Compared with splenic cNK cells, fewer uILC1s produced IFN-γ, although the frequency of IFN-γ+ upon stimulation increased at midgestation (Fig. 5A).

Bottom Line: In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology.Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR(+) and partially overlap with previously described IL-22-producing uterine NK cells.This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Cambridge School of Clinical Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0SW, United Kingdom; jmd83@medschl.cam.ac.uk.

Show MeSH
Related in: MedlinePlus