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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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uILC3 is the major subset in human endometrium and decidua. Top panels show representative data from human endometrium (E) and decidua (D). CD127+ uILCs were gated on CD45+CD3−CD19−CD14− cells and analyzed for intracellular RORγt expression. RORγt+ uILC3s were assessed for NKp44, CD56, and c-kit expression. Bottom panels show percentages of CD127+ uILCs among leukocytes (bottom left), RORγt+ uILC3s among CD127+ cells (bottom middle), and NKp44+ among RORγt+ uILC3s (bottom right) in the E and the D (n = 5 samples for each group, mean, unpaired t test).
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fig01: uILC3 is the major subset in human endometrium and decidua. Top panels show representative data from human endometrium (E) and decidua (D). CD127+ uILCs were gated on CD45+CD3−CD19−CD14− cells and analyzed for intracellular RORγt expression. RORγt+ uILC3s were assessed for NKp44, CD56, and c-kit expression. Bottom panels show percentages of CD127+ uILCs among leukocytes (bottom left), RORγt+ uILC3s among CD127+ cells (bottom middle), and NKp44+ among RORγt+ uILC3s (bottom right) in the E and the D (n = 5 samples for each group, mean, unpaired t test).

Mentions: We analyzed samples obtained from first-trimester decidua and from endometrium of nonpregnant women during the luteal phase. Tissues mechanically dissociated as enzymatic digestion resulted in loss of CD56 and NKp44 expression (data not shown). Human uNK cells have been extensively characterized and, therefore, were not analyzed in this study. CD3−CD19−CD14−CD127+ cells were found in both endometrium and decidua and with similar frequencies (Fig. 1). The vast majority of these cells expressed RORγt, and thus belong to uILC3s (Fig. 1). NCR+ uILC3s was the major subset, expressing also higher levels of CD56 compared with NCR− uILC3s (Fig. 1). Unlike mature uNK cells, uILC3s were found to be c-kit+ and CD9−. CD127+ uILC2s (CD56−RORγt−GATA-3hiCRTH2+) were detectable in three of five samples at a very low frequency (<0.01%; data not shown). No CD127+ uILC1s (RORγt−T-bet+) could be detected in these samples (data not shown). These results demonstrate the presence of a dominant population of NCR+CD127+ uILC3s, with a few NCR− cells. These data confirm a recent study analyzing ILCs in the decidua (23) and show for the first time, to our knowledge, that the uILC composition is similar in nonpregnant endometrium and decidua.


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)

uILC3 is the major subset in human endometrium and decidua. Top panels show representative data from human endometrium (E) and decidua (D). CD127+ uILCs were gated on CD45+CD3−CD19−CD14− cells and analyzed for intracellular RORγt expression. RORγt+ uILC3s were assessed for NKp44, CD56, and c-kit expression. Bottom panels show percentages of CD127+ uILCs among leukocytes (bottom left), RORγt+ uILC3s among CD127+ cells (bottom middle), and NKp44+ among RORγt+ uILC3s (bottom right) in the E and the D (n = 5 samples for each group, mean, unpaired t test).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

fig01: uILC3 is the major subset in human endometrium and decidua. Top panels show representative data from human endometrium (E) and decidua (D). CD127+ uILCs were gated on CD45+CD3−CD19−CD14− cells and analyzed for intracellular RORγt expression. RORγt+ uILC3s were assessed for NKp44, CD56, and c-kit expression. Bottom panels show percentages of CD127+ uILCs among leukocytes (bottom left), RORγt+ uILC3s among CD127+ cells (bottom middle), and NKp44+ among RORγt+ uILC3s (bottom right) in the E and the D (n = 5 samples for each group, mean, unpaired t test).
Mentions: We analyzed samples obtained from first-trimester decidua and from endometrium of nonpregnant women during the luteal phase. Tissues mechanically dissociated as enzymatic digestion resulted in loss of CD56 and NKp44 expression (data not shown). Human uNK cells have been extensively characterized and, therefore, were not analyzed in this study. CD3−CD19−CD14−CD127+ cells were found in both endometrium and decidua and with similar frequencies (Fig. 1). The vast majority of these cells expressed RORγt, and thus belong to uILC3s (Fig. 1). NCR+ uILC3s was the major subset, expressing also higher levels of CD56 compared with NCR− uILC3s (Fig. 1). Unlike mature uNK cells, uILC3s were found to be c-kit+ and CD9−. CD127+ uILC2s (CD56−RORγt−GATA-3hiCRTH2+) were detectable in three of five samples at a very low frequency (<0.01%; data not shown). No CD127+ uILC1s (RORγt−T-bet+) could be detected in these samples (data not shown). These results demonstrate the presence of a dominant population of NCR+CD127+ uILC3s, with a few NCR− cells. These data confirm a recent study analyzing ILCs in the decidua (23) and show for the first time, to our knowledge, that the uILC composition is similar in nonpregnant endometrium and decidua.

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