Melanocyte-secreted fibromodulin constrains skin inflammation in mice injected with lupus serum

Marianna Halasi; Abraham Nyska; Limor Rubin; Yuval Tal; George C Tsokos; Irit Adini

doi:10.1016/j.clim.2022.109055

Melanocyte-secreted fibromodulin constrains skin inflammation in mice injected with lupus serum

Clin Immunol. 2022 Aug:241:109055. doi: 10.1016/j.clim.2022.109055. Epub 2022 May 29.

Authors

Marianna Halasi¹, Abraham Nyska², Limor Rubin³, Yuval Tal⁴, George C Tsokos⁵, Irit Adini⁶

Affiliations

¹ Harvard Medical School, Department of Surgery, Center for Engineering in Medicine & Surgery, Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA. Electronic address: mhalasi@mgh.harvard.edu.
² Sackler School of Medicine, Tel Aviv University, and Consultant in Toxicologic Pathology, Ramat Aviv 69978, Israel. Electronic address: anyska@nyska.net.
³ Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address: limorlaz@hadassah.org.il.
⁴ Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address: yuvalt@hadassah.org.il.
⁵ Harvard Medical School, Department of Medicine, Rheumatology, Beth Israel Deaconess Medical Center, E/CLS, 330 Brookline Ave, Boston, MA 02115, USA. Electronic address: gtsokos@bidmc.harvard.edu.
⁶ Harvard Medical School, Department of Surgery, Center for Engineering in Medicine & Surgery, Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA. Electronic address: iadini@mgh.harvard.edu.

PMID: 35640789
DOI: 10.1016/j.clim.2022.109055

Abstract

Skin pigmentation has been linked to the development, prevalence, and severity of several immune-mediated diseases such as SLE. Here, we asked whether fibromodulin (FMOD), which is highly expressed in skin with light complexion, can explain the known differences in the magnitude of inflammation. C57 mice with different levels of pigmentation and FMOD were injected with human lupus serum to induce skin inflammation. Histopathologic studies revealed that black C57 FMOD+/+ that produce low levels of FMOD and white C57 FMOD -/- mice develop more severe inflammation compared with white FMOD +/+ mice. This study also revealed that dark pigmentation and FMOD deletion correlates with the increased numbers of Langerhans cells. Altogether, we identify low pigmentation and FMOD are linked to low severity of inflammation and approaches to promote FMOD expression should offer clinical benefit.

Keywords: Fibromodulin; Langerhans cells; Lupus serum; Melanocytes; Pigment.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Fibromodulin* / metabolism
Humans
Inflammation* / metabolism
Lupus Erythematosus, Systemic
Melanocytes*
Mice
Skin Pigmentation
Skin* / metabolism
Skin* / pathology

Substances

Fmod protein, mouse
Fibromodulin

Grants and funding

R01 EY024046/EY/NEI NIH HHS/United States