PLX264119

GSE144302: Pulmonary Eosinophilic Granulomatosis with Polyangiitis has IgG4 Plasma Cells and Immunoregulatory Features

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The pathologic findings and immunologic mechanisms in eosinophilic granulomatosis with polyangiitis (EGPA) are poorly understood. To characterize pulmonary EGPAs mechanisms, we examined EGPA paraffin-embedded lung biopsies by immunostaining, RNA sequencing, and reverse transcriptase PCR, compared to normal lung.; EGPA lung infiltrates had eosinophils, alveolar macrophages, B and T cells, plasma cells, basophils, and mast cells. Mast cell degranulation was sparse. PhosphoSMAD2 immunostaining suggests TGF activity.; Using both immunostaining and RNA-sequencing, showed significant increases for both type 2 related genes (CD209,TNFSF14(induces TGF and IL-13)), immunoregulatory genes (FOXP3,CYP27B1(makes calcitriol),ALOX15and particularlyIGHG4). Regulatory T cells and IgG4 plasma cells with IgG4-containing presumed immune complexes coating macrophages, were strikingly abundant relative to controls.HPGD (metabolizes prostaglandins and other eicosanoids) was substantially decreased. RNA studies also showed increased contents of collagen transcripts,IL13,CCL18, andCCL13.; These findings suggest a novel mechanism involving alveolar macrophages, activated by ALOX15-eicosanoid products, making chemokines CCL18 and CCL13 and thus inducing a mixed type 2 plus immunoregulatory immune response. This infiltrate resembles the immune response to an invasive parasite rather than the IgE / mast cell degranulation response to luminal parasites or in asthma and other classic allergies. These findings also suggest new potential treatment targets for EGPA. SOURCE: Edwin Lin (ehlin92@gmail.com) - University of Utah