C1q and HMGB1 reciprocally regulate human macrophage polarization.
A healthy immune system results from a balance of stimulatory and inhibitory pathways that allow effective responses to acute insults, without descending into chronic inflammation. Failed homeostasis is characteristic of autoimmune diseases such as systemic lupus erythematosus. Although HMGB1 induces proinflammatory M1-like macrophage differentiation, we describe a mechanism by which C1q modulates this activity and collaborates with HMGB1 to induce the differentiation of monocytes to anti-inflammatory M2-like macrophages. These anti-inflammatory macrophages are unresponsive to dendritic cell induction factors, effectively removing them from participation in an adaptive immune response. This pathway is mediated through a complex with RAGE and LAIR-1 and depends on relative levels of C1q and HMGB1. Importantly, these data provide insight into a homeostatic mechanism in which C1q and HMGB1 can cooperate to terminate inflammation, and which may be impaired in C1q-deficient patients with autoimmune disease.
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY.
Myoungsun
0000-0002-0655-3859
M
Son
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY.|The Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY.
Amit
A
Porat
Center for Molecular Innovation, The Feinstein Institute for Medical Research, Manhasset, NY.
Mingzhu
M
He
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY.
Jolien
J
Suurmond
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY.
Frances
0000-0001-9393-327X
F
Santiago-Schwarz
Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Ulf
U
Andersson
The Feinstein Institute for Medical Research, Manhasset, NY.
Thomas R
TR
Coleman
Laboratory of Functional Neuroanatomy, and.
Bruce T
BT
Volpe
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY.
Kevin J
KJ
Tracey
Center for Molecular Innovation, The Feinstein Institute for Medical Research, Manhasset, NY.
Yousef
Y
Al-Abed
Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, NY.
Betty
0000-0002-3250-3804
B
Diamond
D002454:Cell Differentiation / Q000276:immunology*; D016764:Cell Polarity; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D015922:Complement C1q
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