| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Converting Enzyme ADAM17 Is Required for Normal Lymphocyte Development1
* Department of Immunology and
Animal Resource Center, St. Jude Children’s Research Hospital, Memphis, TN 38105; and
Pacific Northwest Research Institute, Seattle, WA 98122 and Department of Medicine, University of Washington, Seattle, WA 98195
TNF-
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
Zn/Zn mice and taceZn/Zn 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant AI-39480, Cancer Center Support CORE Grant CA-21765, funds from the American Lebanese Syrian Associated Charities (to D.A.A.V.), and National Institutes of Health Grants DK59778 and DK63363 and funds from the Crohns and Colitis Foundation of America (to P.J.D.).
2 Current Address: Department of Investigative Toxicology, Amgen Incorporated, 1201 Amgen Court West, Seattle, WA 98119.
3 Current address: Department of Pediatrics and Department of Molecular and Integrative Physiology, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109.
4 Address correspondence and reprint requests to Dr. Dario Vignali, Department of Immunology, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38105. E-mail address: dario.vignali{at}stjude.org
5 Abbreviations used in the paper: TACE, TNF--converting enzyme; ADAM, a disintegrin and metalloprotease 17; DN, double negative; DP, double positive; EGFR, epidermal growth factor receptor; PNA, peanut agglutinin; sTNFR, soluble TNFR; SP, single positive; T1, type 1 transition (B cells).
This article has been cited by other articles:
|
|
 |
|
  K. Horiuchi, T. Kimura, T. Miyamoto, K. Miyamoto, H. Akiyama, H. Takaishi, H. Morioka, T. Nakamura, Y. Okada, C. P. Blobel, et al. Conditional Inactivation of TACE by a Sox9 Promoter Leads to Osteoporosis and Increased Granulopoiesis via Dysregulation of IL-17 and G-CSF J. Immunol., February 15, 2009; 182(4): 2093 - 2101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Gelling, W. Yan, S. Al-Noori, A. Pardini, G. J. Morton, K. Ogimoto, M. W. Schwartz, and P. J. Dempsey Deficiency of TNF{alpha} Converting Enzyme (TACE/ADAM17) Causes a Lean, Hypermetabolic Phenotype in Mice Endocrinology, December 1, 2008; 149(12): 6053 - 6064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Tian, X. Wu, C. Chi, M. Han, T. Xu, and Y. Zhuang ADAM10 is essential for proteolytic activation of Notch during thymocyte development Int. Immunol., September 1, 2008; 20(9): 1181 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Briso, O. Dienz, and M. Rincon Cutting Edge: Soluble IL-6R Is Produced by IL-6R Ectodomain Shedding in Activated CD4 T Cells J. Immunol., June 1, 2008; 180(11): 7102 - 7106. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
