title: Pregnancy-induced thymic involution is associated with suppression of chemokines essential for T-lymphoid progenitor homing.
abstract: During normal pregnancy, the thymus undergoes a severe reduction in size and thymocyte output, which may contribute to maternal-fetal tolerance. It is presently unknown whether the pregnancy-induced thymic involution also affects nonlymphoid thymic cell populations and whether these changes in stromal cells play a role in the reduction in thymocyte numbers. Here, we characterize the changes in thymic lymphoid and nonlymphoid cells and show that pregnancy results in a reduction of all major thymic lymphoid cell populations, including the early T-lymphoid progenitors (TLPs) and thymic regulatory T cells. In addition to the thymocytes, the thymic involution also includes all major nonlymphoid cell populations, which show a profound reduction in cell numbers. We also show that during pregnancy, the thymic nonlymphoid cells exhibit decreased expression of chemokines that are essential for TLP homing: CCL25, CXCL12, CCL21, and CCL19. In addition, the expression of these chemokines was substantially downregulated by short-term treatment with progesterone but not estrogen. Collectively, these findings suggest a novel mechanism for the pregnancy-induced reduction in TLP homing and the resulting thymic involution.
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, Tartu University, Tartu, Estonia.
authors.forename: Martti
authors.initials: M
authors.lastname: Laan
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, Tartu University, Tartu, Estonia.
authors.forename: Uku
authors.initials: U
authors.lastname: Haljasorg
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, Tartu University, Tartu, Estonia.
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Institute of Biomedicine and Translational Medicine, Tartu University, Tartu, Estonia.|Competence Centre on Health Technologies, Tartu University, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, Tartu University, Tartu, Estonia.
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
mesh_terms: D000818:Animals; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D019742:Chemokines, CC; D004967:Estrogens; D011374:Progesterone
keywords: Chemokines; Homing; Pregnancy; T-lymphoid progenitor; Thymus; Tolerance