Exploring NKT cell and Perforin-mediated regulation of digit tip regeneration in both male and female adult mice

Nina Greeley

Document Type

Article

Publication Date

Summer 2022

Keywords

JMG

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

Amputated digit tip regeneration is critically regulated by the innate immune system. Innate lymphoid cells such as natural killer (NK) cells have been shown to inhibit regeneration through progenitor cell killing mechanisms. However, the role of upstream NK cell regulators such as natural killer T (NKT) cells has not been accurately described. We hypothesized that NKT cell activity would be affected by glycolipid antigen alpha-Galactosylceramide (alpha-GalCer). Alpha-GalCer was injected into female immunocompetent mice at specific intervals leading up to third phalangeal element (P3) amputation. We also speculated Perforin (Prf1) cytotoxic signaling to be a method NK cells used that suppressed digit tip regeneration. P3 amputations of adult male and female Prf1 lacking immunocompetent mice were conducted. Microcomputed tomography (MicroCT) scanning allowed for analysis of hard and soft tissue of the amputated digit tips. We show that the Prf1 knockout was a negligible factor in digit tip regeneration and that a long-term alpha-GalCer injection regime led to hyporesponsiveness of NKT cells. This communication provides insights into the immunological regulation of adult mice regenerative responses which will guide future efforts to enhance repair in humans.

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