Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice

Autor(es)

Francelin, Carolina ^{[1, 2, 3]} ; Geniseli, Ieda ^[4] ; Nagib, Patricia ^[5] ; Gameiro, Jacy ^[6] ; Savino, Wilson ^{[7, 2]} ; Verinaud, Liana ^[4]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet Microbiol & Immunol, Autoimmune Res Lab, Campinas, SP - Brazil

^[2] Fundacao Oswaldo Cruz, Natl Inst Sci & Technol Neuroimmunomodulat INCT N, Oswaldo Cruz Inst, Rio De Janeiro - Brazil

^[3] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 - USA

^[4] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, UNICAMP, Campinas, SP - Brazil

^[5] Fed Univ Goiania UFG, Inst Trop Pathol & Publ Hlth, Goiania, Go - Brazil

^[6] Fed Univ Juiz de Fora UFJF, Dept Parasitol Microbiol & Immunol, Juiz De Fora - Brazil

^[7] Fundacao Oswaldo Cruz, Oswaldo Cruz Inst, Lab Thymus Res, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROIMMUNOMODULATION; v. 27, n. 1, p. 28-37, JUL 2020.
• Citações Web of Science: 0

Resumo

Background:Previous work revealed the existence of a severe thymic atrophy with massive loss of immature CD4(+)CD8(+) thymocytes in animals developing insulin-dependent diabetes, chemically induced by alloxan. Furthermore, the intrathymic expression of chemokines, such as CXCL12, is changed in these animals, suggesting that cell migration-related patterns may be altered. One molecular interaction involved in normal thymocyte migration is that mediated by soluble semaphorin-3A and its cognate receptor neuropilin-1.Objectives:We investigated herein the expression and role of semaphorin-3A in the migratory responses of thymocytes from alloxan-induced diabetic mice. We characterized semaphorin-3A and its receptor, neuropilin-1, in thymuses from control and diabetic mice as well as semaphorin-3A-dependent migration of developing thymocytes in both control and diabetic animals.Methods:Diabetes was chemically induced after a single injection of alloxan in young adult BALB/c mice. Thymocytes were excised from control and diabetic individuals and subjected to cytofluorometry for simultaneous detection of semaphorin-3A or neuropilin-1 in CD4/CD8-defined subsets. Cell migration in response to semaphorin-3A was performed using cell migration transwell chambers.Results:Confirming previous data, we observed a severe decrease in the total numbers of thymocytes in diabetic mice, which comprised alterations in both immature (double-negative subpopulations) and mature CD4/CD8-defined thymocyte subsets. These were accompanied by a decrease in the absolute numbers of semaphorin-3A-bearing thymocytes, comprising CD4(-)CD8(-), CD4(+)CD8(+), and CD4(-)CD8(+) cells. Additionally, immature CD4(-)CD8(-) and CD4(+)CD8(+) developing T cells exhibited a decrease in the membrane density of semaphorin-3A. The relative and absolute numbers of neuropilin-1-positive thymocytes were also decreased in diabetic mouse thymocytes compared to controls, as seen in CD4(-)CD8(-), CD4(+)CD8(+), and CD4(-)CD8(+) cell subpopulations. Functionally, we observed a decrease in the chemorepulsive role of semaphorin-3A, as revealed by transwell migration chambers. Such an effect was seen in all immature and mature thymocyte subsets.Conclusions:Taken together, our data clearly unravel a disruption in the normal cell migration pattern of developing thymocytes following chemically induced insulin-dependent diabetes, as ascertained by the altered migratory response to sempahorin-3A. In conceptual terms, it is plausible to think that such disturbances in the migration pattern of thymocytes from these diabetic animals may exert an impact in the cell-mediated immune response of these mice. (AU)

• Processo FAPESP: 10/19558-3 - Papel da leptina na atrofia tímica e na resposta imune em animais com diabetes induzida experimentalmente
• Beneficiário: Carolina Francelin de Andrade
• Modalidade de apoio: Bolsas no Brasil - Doutorado