PAM3 Supports the Generation of M2-like Macrophages from Lupus Patient Monocytes and Improves Disease Outcome in Murine Lupus

Overview

Journal J Autoimmun

Specialty Allergy & Immunology

Date 2019 Jan 26

PMID 30679006

Citations 20

Authors

Begum Horuluoglu

Defne Bayik

Neslihan Kayraklioglu

Emilie Goguet

Mariana J Kaplan

Dennis M Klinman

Affiliations

Soon will be listed here.

Abstract

Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages. This raised the possibility of PAM3 being used to normalize the M1:M2 ratio in SLE. Consistent with that possibility, monocytes from lupus patients differentiated into M2-like macrophages when treated with PAM3 in vitro. Furthermore, lupus-prone NZB x NZW F1 mice responded similarly to weekly PAM3 treatment. Normalization of the M2 macrophage frequency was associated with delayed disease progression, decreased autoantibody and inflammatory cytokine synthesis, reduced proteinuria and prolonged survival in NZB x NZW F1 mice. The ability of PAM3 to bias monocyte differentiation in favor of immunosuppressive macrophages may represent a novel approach to the therapy of SLE.

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