In vivo expansion of a CD9+ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation

Ane Orrantia; Enrique Vázquez-De Luis; Gabirel Astarloa-Pando; Iñigo Terrén; Ainhoa Amarilla-Irusta; Diego Polanco-Alonso; Carmen González; Alasne Uranga; Tomás Carrascosa; Juan J Mateos-Mazón; Juan C García-Ruiz; Sergio Callejas; Ana Quintas; Ana Dopazo; Olatz Zenarruzabeitia; Francisco Borrego

doi:10.1016/j.isci.2022.105235

In vivo expansion of a CD9⁺ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation

iScience. 2022 Sep 28;25(10):105235. doi: 10.1016/j.isci.2022.105235. eCollection 2022 Oct 21.

Authors

Ane Orrantia¹, Enrique Vázquez-De Luis², Gabirel Astarloa-Pando¹, Iñigo Terrén¹, Ainhoa Amarilla-Irusta¹, Diego Polanco-Alonso¹, Carmen González³, Alasne Uranga³, Tomás Carrascosa⁴, Juan J Mateos-Mazón⁵, Juan C García-Ruiz⁵, Sergio Callejas², Ana Quintas², Ana Dopazo^{2

6}, Olatz Zenarruzabeitia¹, Francisco Borrego^{1

7}

Affiliations

¹ Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
² Genomics Unit, Spanish National Center for Cardiovascular Research (CNIC), 28029 Madrid, Spain.
³ Biodonostia Health Research Institute, Hematology and Hemotherapy Service, Donostia University Hospital, 20014 Donostia-San Sebastián, Spain.
⁴ Hematological Cancer Group, Biocruces Bizkaia Health Research Institute, Hematology and Hemotherapy Service, Galdakao-Usansolo University Hospital, 48960 Galdakao, Spain.
⁵ Hematological Cancer Group, Biocruces Bizkaia Health Research Institute, Hematology and Hemotherapy Service, Cruces University Hospital, 48903 Barakaldo, Spain.
⁶ CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
⁷ Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain.

Abstract

Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in the gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile, including the expression of CD9. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9^- NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.

Keywords: Health sciences; components of the immune system; immunology; transcriptomics.