Signals via the Adaptor MyD88 in B Cells and DCs Make Distinct and Synergistic Contributions to Immune Activation and Tissue Damage in Lupus

Lino L. Teichmann, Dominik Schenten, Ruslan Medzhitov, Michael Kashgarian, Mark J. Shlomchik

Research output: Contribution to journalArticle

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Abstract

Detection of self nucleic acids by Toll-like receptors (TLR) preciptates autoimmune diseases, including systemic lupus erythematosus (SLE). It remains unknown how TLR signals in specific cell types contribute to distinct manifestations of SLE. Here, we demonstrate that formation of anti-nuclear antibodies in MRL.Faslpr mice entirely depends on the TLR signaling adaptor MyD88 in B cells. Further, MyD88 deficiency in B cells ameliorated nephritis, including antibody-independent interstitial T cell infiltrates, suggesting that nucleic acid-specific B cells activate nephrotoxic T cells. Surprisingly, MyD88 deletion in dendritic cells (DCs) did not affect nephritis, despite the importance of DCs in renal inflammation. In contrast, MyD88 in DCs was critical for dermatitis, revealing a separate pathogenetic mechanism. DC-expressed MyD88 promoted interferon-α production by plasmacytoid DCs, which was associated with Death domain-associated protein 6 upregulation and B lymphopenia. Our findings thus reveal unique immunopathological consequences of MyD88 signaling in B cells and DCs in lupus.

Original languageEnglish (US)
Pages (from-to)528-540
Number of pages13
JournalImmunity
Volume38
Issue number3
DOIs
StatePublished - Mar 21 2013
Externally publishedYes

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Dendritic Cells
B-Lymphocytes
Toll-Like Receptors
Nephritis
Systemic Lupus Erythematosus
Nucleic Acids
T-Lymphocytes
Lymphopenia
Dermatitis
Interferons
Autoimmune Diseases
Anti-Idiotypic Antibodies
Up-Regulation
Inflammation
Kidney
Antibodies
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Signals via the Adaptor MyD88 in B Cells and DCs Make Distinct and Synergistic Contributions to Immune Activation and Tissue Damage in Lupus. / Teichmann, Lino L.; Schenten, Dominik; Medzhitov, Ruslan; Kashgarian, Michael; Shlomchik, Mark J.

In: Immunity, Vol. 38, No. 3, 21.03.2013, p. 528-540.

Research output: Contribution to journalArticle

Teichmann, Lino L. ; Schenten, Dominik ; Medzhitov, Ruslan ; Kashgarian, Michael ; Shlomchik, Mark J. / Signals via the Adaptor MyD88 in B Cells and DCs Make Distinct and Synergistic Contributions to Immune Activation and Tissue Damage in Lupus. In: Immunity. 2013 ; Vol. 38, No. 3. pp. 528-540.
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