Details

Autor(en) / Beteiligte

• Bandyopadhyay, Mohna
• Morelli, Adrian E
• Erdos, Geza
• Sumpter, Tina L
• Tkacheva, Olga A
• Shufesky, William J
• Falo, Louis D
• Larregina, Adriana T

Titel

Restraining neuroinflammation during antigen delivery as an immunosuppressive approach to prevent and treat contact dermatitis

Ist Teil von

• The Journal of immunology (1950), 2019-05, Vol.202 (1_Supplement), p.133-133.6

Erscheinungsjahr

2019

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract Neuroinflammation promotes the initiation and sustains chronic inflammatory disorders. Substance-P, released by sensory neurons, is the prototype neuropeptide that signals via the neurokinin 1 receptor (NK1R) to enhance cellular immunity. We observed that NK1RKO or SPKO mice do not develop contact dermatitis (CD). Hence, we hypothesized that limiting neuroinflammation during Ag entrance induces an immune-suppressive environment to prevent T cell priming and eliminate memory T cells that cause CD. We co-delivered OVA or 2,4-dinitrocholorobencene (DNCB) and two different NK1R antagonists during sensitization of a DTH reaction induced to C57/BL6 mice reconstituted or not with OTI and OTII cells. For efficient skin delivery, we generated microneedle arrays loaded with OVA or DNCB and NK1R antagonists. We demonstrate that our approach prevents the innate and adaptive immunity accounting for the initiation of CD and mitigates pre-existing pathogenic memory T cells that cause local or systemic CD relapses. Mechanistic studies demonstrate that NK1R antagonists suppress the release of pro-inflammatory cytokines in the skin, promote the death of activated CD4 Th1 and CD8 T-cells, and generate Tregs in the skin draining lymph nodes. Our data demonstrates that controlling neuroinflammation during Ag entrance prevents the generation of pathogenic effector and memory T cells accounting for the initiation and relapses of chronic inflammatory skin disorders like CD. NIH R01 AR068249 and AR071277 to ATL and LDF.