B Cells Produce the Tissue-Protective Protein RELMα during Helminth Infection, which Inhibits IL-17 Expression and Limits Emphysema

Abstract

Highlights d Helminth-induced emphysema is IL-17-dependent and exacerbated in B cell-deficient mice d IL-4R signaling triggers activation of B cells that mitigate emphysematous pathology d These B cells express RELMa, which inhibits IL-17-producing gd T cells

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

“…Nb larva typically leave the lung and migrate to the small intestine by day 4 after inoculation (Anthony et al, 2007). The magnitude of the type 2 inflammatory response decreases shortly thereafter but remains potent, resulting in chronic inflammation and the associated development of fibrosis and emphysematous pathology (Chen et al, 2018;Marsland et al, 2008). Mo-AMs expressed high levels of CD11c and SiglecF by day 7, but transcriptome analyses revealed that they were distinct from TD-AMs.…”

Lung macrophages mediate helminth resistance through differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

“…The genetic background of the host may also be of importance and our studies of Mo-AMs have necessarily focused on BL/6 mice as that is the genetic background of the fate mapping mice used in these studies. Previous studies have shown potent type 2 responses to N. brasiliensis in both BL/6 and BALB/c mice 3, 6, 36 . In future studies, the role of Mo-AMs in mediating helminth resistance in mice with varying genetic backgrounds should be investigated.…”

“…Parasites typically leave the lung and migrate to the small intestine by day 4 after inoculation 35 . The magnitude of the type 2 inflammatory response decreases shortly thereafter, but still remains potent, resulting in chronic inflammation and the associated development of fibrosis and emphysematous pathology 36, 37 . Mo-AMs expressed high levels of CD11c and Siglec-F by day 7 but transcriptome analyses revealed that they were distinct from TD-AMs as revealed by PCA and Euclidean distance analyses.…”

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities

“…Indeed, from a clinical perspective, molecules that drive expansion, mobilization, or increased mucosal homing of 9Tregs are the holy grail for many disorders that result from immune dysregulation [57,58], and we will provide defined examples later in this review. Regulatory B cells (Bregs) are also a feature of helminth infections [59] and are the primary source of IL-10 and other tissue-protective proteins, including (Resistin-like molecule-α) RELMα [60,61]. Indeed, in mice infected with H. polygyrus, IL-10 + Breg cells were able to promote expansion and maintenance of IL-10 + FOXP3 + Treg cell populations [61].…”