Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells

Sonya J Wolf; Shannon N Estadt; Jonathan Theros; Tyson Moore; Jason Ellis; Jianhua Liu; Tamra J Reed; Chaim O Jacob; Johann E Gudjonsson; J Michelle Kahlenberg

doi:10.1016/j.jaut.2019.06.002

Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells

J Autoimmun. 2019 Sep:103:102291. doi: 10.1016/j.jaut.2019.06.002. Epub 2019 Jun 24.

Authors

Affiliations

¹ Div. of Rheumatology, Dept. of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Immunology Program, University of Michigan, Ann Arbor, MI, USA.
² Div. of Rheumatology, Dept. of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
³ Immunology Program, University of Michigan, Ann Arbor, MI, USA; Div. of Allergy and Immunology, Dept. of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁴ University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁵ Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
⁶ Div. of Rheumatology, Dept. of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address: [email protected].

Abstract

Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role of type I IFNs in regulating immune cell activation between wild-type and lupus-prone mice following UVB exposure. 10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 100 mJ/cm² of UVB for 5 consecutive days. Following UVB treatment, draining lymph node cell populations were characterized via flow cytometry and suppression assays; treated skin was examined for changes in expression of type I IFN genes. Only NZM2328 mice showed an increase in T cell numbers and activation 2 weeks post UVB exposure. This was preceded by a significant increase in UVB-induced type I IFN expression in NZM2328 mice compared to BALB/c mice. Following UVB exposure, both BALB/c and iNZM mice demonstrated an increase in functional T regulatory (T_Reg) cells; however, this was not seen in NZM2328 mice. These data suggest a skewed UVB-mediated T cell response in lupus-prone mice where activation of T cells is enhanced secondary to a type I IFN-dependent suppression of T_Reg cells. Thus, we propose type I IFNs are important for UVB-induced inflammation in lupus-prone mice and may be an effective target for prevention of UVB-mediated flares.

Keywords: Interferon; Systemic lupus; T cells; T(REGs); Ultraviolet light.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Female
Gene Expression Regulation
Humans
Inflammation / immunology*
Interferon Type I / metabolism*
Lupus Erythematosus, Systemic / immunology*
Lupus Nephritis / immunology*
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Mutant Strains
Radiation Exposure
Skin / pathology*
Skin / radiation effects
T-Lymphocytes, Regulatory / immunology*
Ultraviolet Rays / adverse effects*

Substances

Interferon Type I

Abstract

Publication types

MeSH terms

Substances

Grants and funding