| Full text | |
| Author(s): |
Francelin, Carolina
[1, 2, 3]
;
Geniseli, Ieda
[4]
;
Nagib, Patricia
[5]
;
Gameiro, Jacy
[6]
;
Savino, Wilson
[7, 2]
;
Verinaud, Liana
[4]
Total Authors: 6
|
| Affiliation: | [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
Total Affiliations: 7
|
| Document type: | Journal article |
| Source: | NEUROIMMUNOMODULATION; v. 27, n. 1, p. 28-37, JUL 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 10/19558-3 - Studies in leptin effects in thymus atrophy and immune responses during experimental diabetes |
| Grantee: | Carolina Francelin de Andrade |
| Support Opportunities: | Scholarships in Brazil - Doctorate |