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The role of endogenous glucocorticoids in lymphocyte development in melanocortin receptor 2-deficient mice
Yoshinori Sato1, Harumi Suzuki, Tsuyoshi Sato
1Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Abstract:
Glucocorticoids are extensively used in anti-inflammatory therapy and are thought to contribute to the steady-state regulation of hematopoiesis and lymphopoiesis. We have previously established MC2R(-/-) mice, a model of familial glucocorticoid deficiency, that show several similarities to patients with this disease, including undetectable levels of corticosterone, despite high levels of ACTH and unresponsiveness to ACTH. In this study, we analyzed the possible roles of endogenous glucocorticoids in hematopoiesis and lymphopoiesis in MC2R(-/-) and CRH(-/-) mice as models of chronic adrenal insufficiency. Our analysis of total peripheral blood cell counts revealed that the number of lymphocytes was increased and the number of erythrocytes was slightly, but significantly, decreased in MC2R(-/-) mice. Numbers of immature double negative (CD4(-) CD8(-)) thymocytes, transitional type 1 B cells in the spleen, and pre-B cells in the bone marrow, were significantly increased in MC2R(-/-) mice, suggesting that endogenous glucocorticoids contribute to steady-state regulation of lymphopoiesis. Oral glucocorticoid supplementation reversed peripheral blood cell counts and reduced numbers of T and B cells in the thymus and the spleen. T cells in the thymus and B cells in the spleen were also increased in CRH(-/-) mice, another animal model of chronic adrenal insufficiency. MC2R(-/-) mice were sensitive to age-related thymic involution, but they were resistant to fasting-associated thymic involution. Our data support the idea that endogenous glucocorticoids contribute to stress-induced as well as steady-state regulation of hematopoiesis and lymphopoiesis.
Insights
Endogenous glucocorticoids regulate blood cell production. In mice lacking these hormones, lymphocyte counts increased, while red blood cell counts decreased, impacting hematopoiesis and lymphopoiesis.
Area of Science:
- Endocrinology
- Immunology
- Hematology
Background:
- Glucocorticoids are vital for anti-inflammatory actions and regulating blood cell development (hematopoiesis and lymphopoiesis).
- Familial glucocorticoid deficiency (MC2R(-/-) mice) and chronic adrenal insufficiency (CRH(-/-) mice) serve as models to study endogenous glucocorticoid roles.
Purpose of the Study:
- To investigate the role of endogenous glucocorticoids in steady-state hematopoiesis and lymphopoiesis.
- To analyze the effects of chronic adrenal insufficiency on immune cell populations and development.
Main Methods:
- Analysis of peripheral blood cell counts in MC2R(-/-) and CRH(-/-) mice.
- Flow cytometry to assess thymocyte and splenic B cell populations.
- Evaluation of glucocorticoid supplementation effects and thymic involution resistance/sensitivity.
Main Results:
- MC2R(-/-) mice exhibited increased lymphocytes, decreased erythrocytes, and elevated immature thymocytes, transitional B cells, and pre-B cells.
- Glucocorticoid supplementation normalized blood counts and reduced T and B cell populations in thymus and spleen.
- CRH(-/-) mice also showed increased T and B cells, indicating a broader role for glucocorticoids.
Conclusions:
- Endogenous glucocorticoids are crucial for the steady-state regulation of hematopoiesis and lymphopoiesis.
- These hormones play a role in both normal blood cell maintenance and stress-induced responses affecting the immune system.
