Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

Abstract

Abbreviations: Ab, antibody; AD, atopic dermatitis; Ag, antigen; Arg1, arginase 1; CCR4, C-C chemokine receptor type 4; CD, cluster of differentiation; CXCR3, C-X-C chemokine receptor type 3; ELISA, enzyme-linked immunosorbent assay; IENFD, intraepidermal nerve fiber density; Ig, immunoglobulin; IL, interleukin; IL-7Rα, IL-7 receptor α; iNOS, inducible nitric oxide synthase; OSMRβ, oncostatin M receptor β; PAR-2, protease-activated receptor 2; PGP9.5, protein gene product 9.5; pM, peritoneal macrophages; TARC, thymus and activationregulated chemokine; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor. Abstract Background: Scabies is a common contagious skin disease caused by an infestation of the skin by Sarcoptes scabiei var. hominis. A hallmark symptom of scabies is severe itch. Methods: We sought to determine the generation of a pruritogenic cytokine, interleukin (IL)-31, together with immune profiles in skin lesions of ordinary scabies through immunohistochemical and immunofluorescent studies. To elucidate the pathological mechanisms of IL-31 generation, murine peritoneal macrophages were stimulated with various T helper 2 (Th2) cytokines and proteins ex vivo. Results: A large number of CCR4(+) Th2 cells, eosinophils, and basophils infiltrated in scabies lesions. Increased generation of IL-31, thymic stromal lymphopoietin (TSLP), and periostin was also observed. A major population of IL-31(+) cells were Arginase-1(+)/CD163(+) M2 macrophages. Murine peritoneal macrophages showed an M2 phenotype and generated IL-31 when stimulated with TSLP and periostin.Conclusion: IL-31 appeared to be largely generated by M2 macrophages in ordinary scabies lesions. This IL-31 induction was mediated by TSLP and periostin. K E Y W O R D SIL-31, macrophage, periostin, scabies, thymic stromal lymphopoietin

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

“…Under such abundant triggers and regulators, TSLP succeeds in sensing both exogenous and endogenous dangerous signals and exacerbating allergic inflammation as an alarm via activating its downstream responders, namely naive Th cells, Th2 cells, ILC2s, and myeloid dendritic cells 72,80‐82 . TSLP activates myeloid DCs (mDCs) via ligation to its heterodimer receptor on mDCs and subsequently upregulates the expression of the co‐stimulatory molecule OX40L, namely the ligand for OX40 on CD4 + T cells, which results in the induction of Th2 differentiation 83 .…”

Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages

“…Periostin, substance P, and hemosiderin, but not thymic stromal lymphopoietin, are correlated with IL-31 expression by macrophages Thymic stromal lymphopoietin and periostin promote M2 skewing (Furudate et al, 2016;Han et al, 2013) and IL-31 generation from M2 macrophages (Hashimoto et al, 2019b). Epidermal expression of thymic stromal lymphopoietin was not enhanced in the SD lesions compared with healthy controls (t-test, P ¼ 0.182).…”

“…Macrophages are generally divided into two groups: M1 and M2 (Wang et al, 2014). Our group previously reported that M2 macrophages are capable of generating IL-31 (Hashimoto et al, 2019b). Thus, we examined the expression of an M2 marker, CD163, by CD68(þ) cells.…”

“…To elucidate the mechanisms of IL-31-generation from macrophages, we employed an ex vivo stimulation test with murine peritoneal macrophages (pM) (Hashimoto et al, 2019b). pM were stimulated with substance P, periostin, and/or RBC lysate, which represents hemosiderin.…”

The Skin Microbiota and Itch: Is There a Link?

“…Th2 immunity is dominant in scabies and is complemented by a heavy inflow of IL-31(+) M2 macrophages [73]. Proteases from scabies mite stir epidermal KCs to express TSLP.…”