TNF, but not IL-6 and IL-17, is crucial for the development of T cell-independent psoriasis-like dermatitis in Il1rn-/- mice.

Abstract

IL-1 is a proinflammatory cytokine consisting of two molecular species, IL-1alpha and IL-1beta, and IL-1R antagonist (gene: Il1rn) is the endogenous suppressor. Il1rn(-/-) mice spontaneously develop autoimmune diseases, such as arthritis and aortitis, and a dermatitis that histologically resembles human psoriasis. The pathogenic mechanisms underlying this dermatitis, however, remain to be elucidated. In this study, we demonstrated that the production of inflammatory cytokines and chemokines was enhanced at the site of inflammation. The development of dermatitis was completely suppressed in Tnfsf1a(-/-) but not in Il6(-/-) mice, similar to that observed in arthritis and aortitis. However, IL-17 deficiency did not affect the development of dermatitis at all, in clear contrast to that of arthritis and aortitis. Different from arthritis and aortitis, adoptive transfer of Il1rn(-/-) T cells did not induce dermatitis in the recipient SCID mice and skin lesions developed in Il1rn(-/-) SCID mice, indicating that T cells are not involved in the development of skin lesions. In support for this, bone marrow cell transplantation experiments showed that TNF produced by skin residential cells, but not bone marrow cell-derived cells, was important for the development of dermatitis. Furthermore, we showed that IL-1 directly enhanced TNF and chemokine expression in keratinocytes. These observations suggest that excess IL-1 signaling directly activates keratinocytes to produce TNF and chemokines, resulting in the development of psoriasis-like skin lesions without the involvement of autoimmunity in Il1rn(-/-) mice.

• Authors: Akiko Nakajima, Taizo Matsuki, Mayumi Komine, Akihiko Asahina, Reiko Horai, Susumu Nakae, Harumichi Ishigame, Shigeru Kakuta, Shinobu Saijo, Yoichiro Iwakura
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 3 Pg. 1887-93 (Aug 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20610641 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Il1rn protein, mouse
• Inflammation Mediators
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-17
• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Dermatitis, Contact (immunology, metabolism, pathology)
• Female
• Inflammation Mediators (metabolism, physiology)
• Interleukin 1 Receptor Antagonist Protein (deficiency, genetics)
• Interleukin-17 (deficiency, genetics, physiology)
• Interleukin-6 (deficiency, genetics, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Mice, SCID
• Psoriasis (immunology, metabolism, pathology)
• Skin (immunology, metabolism, pathology)
• T-Lymphocyte Subsets (immunology, pathology, transplantation)
• Tumor Necrosis Factor-alpha (biosynthesis, physiology)