This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mühlfeld, A. S. Articles by Alpers, C. E. Search for Related Content PubMed PubMed Citation Articles by Mühlfeld, A. S. Articles by Alpers, C. E.

(American Journal of Pathology. 2003;163:1127-1136.)
© 2003 American Society for Investigative Pathology

Deletion of the Fc Receptor IIb in Thymic Stromal Lymphopoietin Transgenic Mice Aggravates Membranoproliferative Glomerulonephritis

Anja S. Mühlfeld^*, Stephan Segerer, Kelly Hudkins^*, Matthew D. Carling^*, Min Wen^*, Andrew G. Farr, Jeffrey V. Ravetch^¶ and Charles E. Alpers^*

From the Departments of Pathology^* and Biological Structure, University of Washington, Seattle, Washington; the Laboratory of Molecular Genetics and Immunology,^¶ Rockefeller University, New York, New York; the Division of Nephrology and Immunology, University of Aachen, Aachen, Germany; and the Medizinische Poliklinik, Klinikum der Innenstadt, University of Munich, Munich, Germany

Engagement of immunoglobulin-binding receptors (FcR) on leukocytes and other cell types is one means by which immunoglobulins and immune complexes activate effector cells. One of these FcRs, FcRIIb, is thought to contribute to protection from autoimmune disease by down-regulation of B-cell responsiveness and myeloid cell activation. We assessed the role of FcRIIb in a mouse model of cryoglobulin-associated membranoproliferative glomerulonephritis induced by overexpression of thymic stromal lymphopoietin (TSLP). TSLP transgenic mice were crossbred with animals deficient for FcRIIb on the same genetic background (C57BL/6). Renal pathology was assessed in female and male animals (wild-type, FcRIIb-/-, TSLP transgenic, and combined TSLP transgenic/FcRIIb-/- mice) after 50 and 120 days, respectively. FcRIIb-/- mice had no significant renal pathology, whereas overexpression of TSLP induced a membranoproliferative glomerulonephritis, as previously established. TSLP transgenic FcRIIb-/- mice appeared sick with increased mortality. Kidney function was significantly impaired in male mice corresponding to aggravated glomerular pathology with increases in glomerular matrix and cellularity. This resulted from both a large influx of infiltrating macrophages and increased cellular proliferation. These results emphasize the important role of FcRIIb in regulating immune responses and suggest that modulation of Fc receptor activation or expression may be a useful therapeutic approach for treating glomerular diseases.

This article has been cited by other articles:

				S. Guo, J. Kowalewska, T. A. Wietecha, M. Iyoda, L. Wang, K. Yi, M. Spencer, M. Banas, S. Alexandrescu, K. L. Hudkins, et al. Renin-Angiotensin System Blockade Is Renoprotective in Immune Complex-Mediated Glomerulonephritis J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1168 - 1176. [Abstract] [Full Text] [PDF]

				M. C. Banas, B. Banas, K. L. Hudkins, T. A. Wietecha, M. Iyoda, E. Bock, P. Hauser, J. W. Pippin, S. J. Shankland, K. D. Smith, et al. TLR4 Links Podocytes with the Innate Immune System to Mediate Glomerular Injury J. Am. Soc. Nephrol., April 1, 2008; 19(4): 704 - 713. [Abstract] [Full Text] [PDF]

				S. Taneda, K. L. Hudkins, A. S. Muhlfeld, J. Kowalewska, J. W. Pippin, S. J. Shankland, and C. E. Alpers Protease Nexin-1, tPA, and PAI-1 are Upregulated in Cryoglobulinemic Membranoproliferative Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 243 - 251. [Full Text] [PDF]

				C. E. Alpers and J. Kowalewska Emerging Paradigms in the Renal Pathology of Viral Diseases Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(Supplement_1): S6 - S12. [Abstract] [Full Text] [PDF]

				X. Feng, H. Li, A. A. Rumbin, X. Wang, A. La Cava, K. Brechtelsbauer, L. W. Castellani, J. L. Witztum, A. J. Lusis, and B. P. Tsao ApoE-/-Fas-/- C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia J. Lipid Res., April 1, 2007; 48(4): 794 - 805. [Abstract] [Full Text] [PDF]

				J. Kowalewska, A. S. Muhlfeld, K. L. Hudkins, M. M. Yeh, A. G. Farr, J. V. Ravetch, and C. E. Alpers Thymic Stromal Lymphopoietin Transgenic Mice Develop Cryoglobulinemia and Hepatitis with Similarities to Human Hepatitis C Liver Disease Am. J. Pathol., March 1, 2007; 170(3): 981 - 989. [Abstract] [Full Text] [PDF]

				D. E. Sloane, N. Tedla, M. Awoniyi, D. W. MacGlashan Jr, L. Borges, K. F. Austen, and J. P. Arm Leukocyte immunoglobulin-like receptors: novel innate receptors for human basophil activation and inhibition Blood, November 1, 2004; 104(9): 2832 - 2839. [Abstract] [Full Text] [PDF]