Lack of the long pentraxin PTX3 promotes autoimmune lung disease but not glomerulonephritis in murine systemic lupus erythematosus

Maciej Lech, Christoph Römmele, Onkar P. Kulkarni, Heni Eka Susanti, Adriana Migliorini, Cecilia Garlanda, Alberto Mantovani, Hans Joachim Anders

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated recruitment of leukocytes. Both of these mechanisms are known to be involved in autoimmunity and autoimmune tissue injury, e.g. in systemic lupus erythematosus, but a contribution of PTX3 is hypothetical. To evaluate a potential immunoregulatory role of PTX3 in autoimmunity we crossed Ptx3-deficient mice with Fas-deficient (lpr) C57BL/6 (B6) mice with mild lupus-like autoimmunity. PTX3 was found to be increasingly expressed in kidneys and lungs of B6lpr along disease progression. Lack of PTX3 impaired the phagocytic uptake of apoptotic T cells into peritoneal macrophages and selectively expanded CD4/CD8 double negative T cells while other immune cell subsets and lupus autoantibody production remained unaffected. Lack of PTX3 also aggravated autoimmune lung disease, i.e. peribronchial and perivascular CD3+ T cell and macrophage infiltrates of B6lpr mice. In contrast, histomorphological and functional parameters of lupus nephritis remained unaffected by the Ptx3 genotype. Together, PTX3 specifically suppresses autoimmune lung disease that is associated with systemic lupus erythematosus. Vice versa, loss-of-function mutations in the Ptx3 gene might represent a genetic risk factor for pulmonary (but not renal) manifestations of systemic lupus or other autoimmune diseases.

Original languageEnglish
Article numbere20118
JournalPLoS One
Volume6
Issue number5
DOIs
Publication statusPublished - 2011

Fingerprint

lupus erythematosus
glomerulonephritis
Pulmonary diseases
autoimmunity
T-cells
Glomerulonephritis
Autoimmunity
Systemic Lupus Erythematosus
respiratory tract diseases
Lung Diseases
Autoimmune Diseases
T-lymphocytes
Macrophages
T-Lymphocytes
mice
macrophages
lungs
kidneys
Kidney
Lung

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lack of the long pentraxin PTX3 promotes autoimmune lung disease but not glomerulonephritis in murine systemic lupus erythematosus. / Lech, Maciej; Römmele, Christoph; Kulkarni, Onkar P.; Susanti, Heni Eka; Migliorini, Adriana; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans Joachim.

In: PLoS One, Vol. 6, No. 5, e20118, 2011.

Research output: Contribution to journalArticle

Lech, Maciej ; Römmele, Christoph ; Kulkarni, Onkar P. ; Susanti, Heni Eka ; Migliorini, Adriana ; Garlanda, Cecilia ; Mantovani, Alberto ; Anders, Hans Joachim. / Lack of the long pentraxin PTX3 promotes autoimmune lung disease but not glomerulonephritis in murine systemic lupus erythematosus. In: PLoS One. 2011 ; Vol. 6, No. 5.
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