title: Interleukin 7 plays a role in T lymphocyte apoptosis inhibition driven by mesenchymal stem cell without favoring proliferation and cytokines secretion.
abstract: Since 2004, when a case report describing the use of human mesenchymal stem cells (hMSCs) infusion as a therapy for GVHD after bone marrow transplantation, a new perspective in MSC function emerged. Since then hMSCs immunomodulatory potential became the target of several studies. Although great progress has been made in our understanding of hMSCs, their effect on T cell remains obscure. Our study has confirmed the already described effect of hMSCs on lymphocytes proliferation and survival. We also show that the impairment of lymphocyte proliferation and apoptosis is contact-independent and occurs in a prostaglandin-independent manner. A potential correlation between IL-7 and hMSCs effect is suggested, as we observed an increase in IL-7 receptors (CD127) on lymphocyte membrane in MSC presence. Additionally, blocking IL-7 in hMSCs-lymphocytes co-cultures increased lymphocytes apoptosis and we also have demonstrated that hMSCs are able to produce this interleukin. Moreover, we found that during Th1/Th17 differentiation in vitro, hMSCs presence leads to Th1/Th17 cells with reduced capacity of INF-y and IL-17 secretion respectively, regardless of having several pro-inflammatory cytokines in culture. We did not confirm an increment of Treg in these cultures, but a reduced percentage of INF-y/IL-17 secreting cells was observed, suggesting that the ratio between anti and pro-inflammatory cells changed. This changed ratio is very important to GvHD therapy and links hMSCs to an anti-inflammatory role. Taken together, our findings provide important preliminary results on the lymphocyte pathway modulated by MSCs and may contribute for developing novel treatments and therapeutic targets for GvHD and others autoimmune diseases.
authors.affiliation: Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEP-AE), São Paulo, SP, Brasil; Programa de Pós-graduação em Alergia e Imunopatologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Normanton
authors.affiliation: Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEP-AE), São Paulo, SP, Brasil; Programa de Pós-graduação em Alergia e Imunopatologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil.
authors.forename: Heliene
authors.initials: H
authors.lastname: Alvarenga
authors.affiliation: Hospital Israelita Albert Einstein, Bone Marrow Transplant Program, São Paulo, SP, Brasil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Hamerschlak
authors.affiliation: Hospital Israelita Albert Einstein, Oncology Department, São Paulo, SP, Brasil.
authors.forename: Andreza
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: Hospital Israelita Albert Einstein, Blood Bank Department, São Paulo, SP, Brasil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEP-AE), São Paulo, SP, Brasil.
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.affiliation: Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEP-AE), São Paulo, SP, Brasil; Programa de Pós-graduação em Alergia e Imunopatologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil.
authors.forename: Luciana Cavalheiro
authors.initials: LC
authors.lastname: Marti
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D058948:Cell Tracking; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells
chemical_list: D016207:Cytokines; C508605:IL7 protein, human; D020381:Interleukin-17; D015851:Interleukin-7; D020395:Receptors, Interleukin-7