Interleukin‐7 in the transition of bone marrow progenitors to the thymus

Abstract

Interleukin-7 (IL-7) is essential for the development of T cells in humans and mice where deficiencies in IL-7 signaling result in severe immunodeficiency. T cells require IL-7 at multiple points during development; however, it is unclear when IL-7 is first necessary. We observed that mice with impaired IL-7 signaling had a large reduction in the number of early thymic progenitors (ETPs) while mice that overexpress IL-7 had greatly increased numbers of ETPs. These results indicated that the development of ETPs is sensitive to IL-7. Bone marrow progenitors of ETP are present in normal numbers in mice with impaired IL-7 signaling (IL-7Rα) and were efficiently recruited to the thymus. Furthermore, ETPs and their progenitors from IL-7Rα mice did not undergo increased apoptosis and proliferate normally compared to WT cells. Mixed bone marrow chimeras demonstrated that IL-7 signaling has a cell-intrinsic role in ETP development but was not required for development of bone marrow progenitors. We have shown a novel role for IL-7 signaling in the development of ETPs that is distinct from classic mechanisms of IL-7 regulating survival and proliferation.

IL-7R–Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis

“…In thymic T cell development, survival and proliferation were most affected in early thymocytes at DN2 stages in IL-7R-Y449F mice, consistent with a previous report (16,27). Coincidently, development of early thymocytes at ETP to DN2 stages, which expressed higher levels of IL-7Ra in DN thymocyte, was transiently impaired in IL-7R-M452L mice.…”

Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis

“…The biological effects of IL-7 on T-cell lymphopoiesis vary for different lineages during the stages of differentiation. Recent studies have shown that the number of early thymic progenitors (ETPs) in mice with impaired IL-7 signaling was significantly decreased, while the number of ETPs in mice with overexpression of IL-7 was greatly increased ( 11 ). The findings indicate that IL-7 can promote the development of ETPs.…”

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

“…Bone marrow-residing cells, such as leukocytes, hematopoietic stem cells (HSCs), and stromal cells, secrete cytokines that are important for the development and function of different immune cells. For example, interleukin (IL) -7 is involved in transition of bone marrow progenitor cells to thymus [ 33 ] and bone marrow stromal cell-secreted IL-7 is essential for early B cell development [ 34 , 35 ]. IL-15, secreted by bone marrow stromal cells [ 36 ], can inhibit IL-7 receptor α-chain, which is needed for T cell differentiation [ 37 ].…”