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

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.