IL-7 is a critical factor in modulating lesion development in Skn-directed autoimmunity

Area of Science:

• Immunology
• Dermatology
• Autoimmunity

Background:

• Adoptive transfer of Skn-immune T cells induces skin lesions in mice with epidermal autoimmunity.
• Peripheral regulation of Skn-induced autoreactivity is disrupted in immunoincompetent models.

Purpose of the Study:

• To investigate the peripheral mechanisms regulating Skn-induced autoimmunity in an immunoincompetent murine model.
• To identify the specific cell types and molecular factors involved in restoring immune tolerance.

Main Methods:

• Adoptive transfer of Skn-immune T cells and normal syngeneic spleen cells into immunosuppressed recipients.
• Enrichment and depletion of CD4+ and CD8+ T cells from spleen cell inoculums.
• RT-PCR analysis for cytokine expression (including IL-7).
• Treatment with anti-IL-7 antibody and topical delivery of an IL-7 encoding plasmid.

Main Results:

• Cotransfer of normal spleen cells significantly reduced lesion severity in Skn-induced autoimmune mice.
• CD4+ T cells were identified as the primary regulatory cells in the cotransfer inoculum.
• Reduced lesion severity correlated with increased Interleukin-7 (IL-7) levels.
• Blocking IL-7 with an antibody abrogated the regulatory effect of normal spleen cells.
• Topical delivery of an IL-7 encoding plasmid suppressed lesion severity independently.

Conclusions:

• CD4+ T cells play a crucial role in the peripheral regulation of Skn-induced skin autoimmunity.
• Interleukin-7 (IL-7) is a key mediator in this regulatory process, working in conjunction with CD4+ T cells.
• These findings elucidate a novel mechanism involving CD4+ T cells and IL-7 for controlling autoreactivity in the skin.