Natural killer (NK) cells are bone marrow–derived granular lymphocytes that have a key role in immune defense against viral and bacterial infections and malignancies. NK cells are traditionally defined as cells of the innate immune response because they lack RAG recombinase–dependent clonal antigen receptors.  However, increasing evidence suggests that NK cells can display several features that are usually attributed to adaptive immune cells, such as memory.  Now, a study led by researchers at the University of Bonn decodes a new mechanism of how NK cells can specifically attack pigmented cells of the skin using memory. The team state that their results may provide new insights into the development of the skin-depigmenting disease vitiligo and offer new options for the treatment of malignant melanoma. These opensource study is published in the journal Immunity.

Previous studies show that pigmented cells of the skin are crucial as a protective shield against UV-radiation. An often-desired suntan can only form with the aid of the enzyme tyrosinase inside these pigmented cells.  The compound monobenzone can specifically block tyrosinase and thereby trigger a stress reaction. As a result, the immune system attacks the affected pigmented cells. A frequent consequence is vitiligo, which leads to milky-white unpigmented areas on the skin.  Scientific studies have shown that people with vitiligo are at lower risk of developing malignant melanoma. A possible method for treating this type of cancer could involve actively triggering vitiligo with the tyrosinase blocker monobenzone.  However, the initial mechanism by which the immune system identifies the monobenzone-exposed pigmented cells as dangerous, before attacking them, has been unclear so far.  The current study explores this path in detail in mice.

The current study utilises mice that are not able to form any functional T and B lymphocytes and applied low doses of monobenzone several times in succession on the rodents’ skin.  Results show that white spots still developed in the animals’ fur, and previously transferred malignant melanoma cells were destroyed, because the mice’s natural killer cells remembered and attacked the pigmented cells.  Data findings show that the multiple monobenzone exposures induced only natural killer cells to recognize and attack the pigmented cells.

Results show that in order for this immune response to occur, an immune-checkpoint had to give the green light first, namely the NLRP3 inflammasome.  The lab explain that this is a protein complex that integrates multiple pieces of signalling information in macrophages, special phagocytes that reside in tissues. They go on to add that once switched on, macrophages then decide whether immune cells including natural killer cells receive their marching orders.

The team surmise that their results show that these NK immune cells can indeed remember pigmented cells when they come into more frequent contact with a specific contact allergen.  For the future, the researchers state that their results may open up new therapeutic avenues for the treatment of malignant melanoma, demonstrate a new type of immune recognition and could even shed new light on the development of vitiligo.

Source: University of Bonn