Secreted IgM modulates IL-10 expression in B cells.

IL-10 B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10 B cell differentiation are ill-defined. Here we find that IL-10 B cells expand in mice lacking secreted IgM ((s)IgM) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10 B cell increase is polyclonal and presents within 24 hours of birth.

Skin-Homing Regulatory B Cells Required for Suppression of Cutaneous Inflammation.

Pro and anti-inflammatory B-cell subsets that localize to unperturbed and inflamed skin are newly emerging components of the skin immune system. To test the relevance of regulatory B cells (Bregs) in the suppression of cutaneous inflammation, we asked whether impaired migration of these cells into the skin exacerbates skin inflammation. Using a mouse model with a B-cell‒specific tamoxifen-inducible deletion of α4β1 integrin, we demonstrate that selective disruption of α4β1-integrin expression in B cells significantly decreases IL-10 Bregs in inflamed skin, whereas it does not affect their counterparts in lymphoid tissues.

Caspase 1/11 Deficiency or Pharmacological Inhibition Mitigates Psoriasis-Like Phenotype in Mice.

Inflammatory caspases, activated within the inflammasome, are responsible for the maturation and secretion of IL-1β/IL-18. Although their expression in psoriasis was shown several years ago, little is known about the role of inflammatory caspases in the context of psoriasis. Here, we confirmed that caspases 1, 4, and 5 are activated in lesional skin from psoriasis patients.

Lysosomal Cholesterol Hydrolysis Couples Efferocytosis to Anti-Inflammatory Oxysterol Production.

Rationale: Macrophages face a substantial amount of cholesterol after the ingestion of apoptotic cells, and the LIPA (lysosomal acid lipase) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment.

Objective: Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo.

Methods And Results: We show that LIPA inhibition causes a defective efferocytic response because of impaired generation of 25-hydroxycholesterol and 27-hydroxycholesterol.