Non-cell autonomous expression of TNF-alpha-converting enzyme ADAM17 is required for normal lymphocyte development.

Li N, Boyd K, Dempsey PJ, Vignali DA
J Immunol. 2007 178 (7): 4214-21

PMID: 17371977 · DOI:10.4049/jimmunol.178.7.4214

TNF-alpha converting enzyme (TACE; ADAM17), a member of the ADAM (a disintegrin and metalloprotease) family of metalloproteases, has been shown to cleave a wide variety of cell surface proteins of immunological importance. Due to the broad expression of TACE and the early postnatal lethality of TACE-deficient mice, it has been difficult to assess the role of TACE in lymphocyte development. Indeed, it is not known whether hemopoietic and/or nonhemopoietic expression of TACE is required for normal lymphocyte development. In the current study, we analyzed the lymphoid system of tace(DeltaZn/DeltaZn) mice and tace(DeltaZn/DeltaZn) bone marrow RAG1(-/-) recipients. Our results clearly show that nonlymphocyte expression of TACE is required for normal lymphocyte development and lymphoid organ structure. Lack of TACE function resulted in a partial block in T cell development at the double-negative 4:double-positive transition in the thymus, a loss of B cell development/maturation in the spleen, and a lack of B cell follicle and germinal center formation in the spleen. Thus, TACE serves as a lymphocyte extrinsic factor that is essential for normal T development and peripheral B cell maturation.

MeSH Terms (11)

ADAM17 Protein ADAM Proteins Animals B-Lymphocytes Bone Marrow Transplantation Homeodomain Proteins Lymphocyte Activation Mice Mice, Mutant Strains Spleen T-Lymphocytes

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