Basophils and the T Helper 2 Environment Can Promote the Development of Lupus Nephritis

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2010 Jun 1

PMID 20512127

Citations 157

Authors

Nicolas Charles

Donna Hardwick

Eric Daugas

Gabor G Illei

Juan Rivera

Affiliations

Soon will be listed here.

Abstract

In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of subjects with SLE. Thus, in Lyn(-/-) mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in individuals with SLE IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis.

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References

Chen K, Xu W, Wilson M, He B, Miller N, Bengten E . Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol. 2009; 10(8):889-98. PMC: 2785232. DOI: 10.1038/ni.1748. View

Peng S, Szabo S, Glimcher L . T-bet regulates IgG class switching and pathogenic autoantibody production. Proc Natl Acad Sci U S A. 2002; 99(8):5545-50. PMC: 122806. DOI: 10.1073/pnas.082114899. View

Seshan S, Jennette J . Renal disease in systemic lupus erythematosus with emphasis on classification of lupus glomerulonephritis: advances and implications. Arch Pathol Lab Med. 2009; 133(2):233-48. DOI: 10.5858/133.2.233. View

Tsuiji M, Yurasov S, Velinzon K, Thomas S, Nussenzweig M, Wardemann H . A checkpoint for autoreactivity in human IgM+ memory B cell development. J Exp Med. 2006; 203(2):393-400. PMC: 2118214. DOI: 10.1084/jem.20052033. View

Atta A, Sousa C, Carvalho E, Sousa-Atta M . Immunoglobulin E and systemic lupus erythematosus. Braz J Med Biol Res. 2004; 37(10):1497-501. DOI: 10.1590/s0100-879x2004001000008. View

Burmeister Getz E, Fisher D, Fuller R . Human pharmacokinetics/pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma. J Clin Pharmacol. 2009; 49(9):1025-36. DOI: 10.1177/0091270009341183. View

Hibbs M, Tarlinton D, Armes J, Grail D, Hodgson G, Maglitto R . Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell. 1995; 83(2):301-11. DOI: 10.1016/0092-8674(95)90171-x. View

Akahoshi M, Nakashima H, Tanaka Y, Kohsaka T, Nagano S, Ohgami E . Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum. 1999; 42(8):1644-8. DOI: 10.1002/1529-0131(199908)42:8<1644::AID-ANR12>3.0.CO;2-L. View

De Carli M, DElios M, Zancuoghi G, Romagnani S, Del Prete G . Human Th1 and Th2 cells: functional properties, regulation of development and role in autoimmunity. Autoimmunity. 1994; 18(4):301-8. DOI: 10.3109/08916939409009532. View

10.

Shimizu S, Sugiyama N, Masutani K, Sadanaga A, Miyazaki Y, Inoue Y . Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). J Immunol. 2005; 175(11):7185-92. DOI: 10.4049/jimmunol.175.11.7185. View

11.

Beavitt S, Harder K, Kemp J, Jones J, Quilici C, Casagranda F . Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity. J Immunol. 2005; 175(3):1867-75. DOI: 10.4049/jimmunol.175.3.1867. View

12.

Kalesnikoff J, Huber M, Lam V, Damen J, Zhang J, Siraganian R . Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity. 2001; 14(6):801-11. DOI: 10.1016/s1074-7613(01)00159-5. View

13.

Miyajima H, Abe K, Ushiyama C, Okumura K, OVARY Z, Hirano T . IgE allotypes in sera of mice with autoimmune diseases and in mice with graft-versus-host disease after transfusion or bone marrow transplantation. Int Arch Allergy Immunol. 1996; 111(2):152-5. DOI: 10.1159/000237360. View

14.

Charles N, Watford W, Ramos H, Hellman L, Oettgen H, Gomez G . Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation. Immunity. 2009; 30(4):533-43. PMC: 2772996. DOI: 10.1016/j.immuni.2009.02.008. View

15.

Singh R, Ebling F, Sercarz E, Hahn B . Immune tolerance to autoantibody-derived peptides delays development of autoimmunity in murine lupus. J Clin Invest. 1995; 96(6):2990-6. PMC: 186011. DOI: 10.1172/JCI118371. View

16.

Mukai K, Matsuoka K, Taya C, Suzuki H, Yokozeki H, Nishioka K . Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity. 2005; 23(2):191-202. DOI: 10.1016/j.immuni.2005.06.011. View

17.

Lee H, Hong Y, Yun H, Kim Y, Kim J, Yoo W . Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus. Rheumatology (Oxford). 2008; 47(6):789-94. DOI: 10.1093/rheumatology/ken108. View

18.

Tiller T, Tsuiji M, Yurasov S, Velinzon K, Nussenzweig M, Wardemann H . Autoreactivity in human IgG+ memory B cells. Immunity. 2007; 26(2):205-13. PMC: 1839941. DOI: 10.1016/j.immuni.2007.01.009. View

19.

Kopf M, Le Gros G, Bachmann M, Lamers M, Bluethmann H, Kohler G . Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993; 362(6417):245-8. DOI: 10.1038/362245a0. View

20.

Peng S, Moslehi J, Craft J . Roles of interferon-gamma and interleukin-4 in murine lupus. J Clin Invest. 1997; 99(8):1936-46. PMC: 508018. DOI: 10.1172/JCI119361. View