Understanding Hidradenitis Suppurativa: New insights into an autoimmune skin condition

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Image credit: https://openai.com/index/dall-e/

Hidradenitis suppurativa (HS) is a nasty, long-term skin problem that can be very difficult to treat. It causes painful lumps, boils, and tunnels under the skin, especially in areas like the armpits and groin. It's different from other skin conditions, as it affects not just the surface but also deeper layers of the skin. Scientists have been working hard to understand what causes it, and recent research is shedding light on some important factors.

What are tertiary lymphoid structures?

One of the key findings is the presence of structures called tertiary lymphoid structures (TLSs) in the skin of people with HS. These TLSs are like little hubs of immune activity that form in response to inflammation. Normally, they're not found in healthy skin, but in HS, they appear near the tunnels that form in the skin. Within these TLSs, immune cells like T cells and B cells gather and start to multiply. This leads to a build-up of inflammation, which is a hallmark of HS.

Key immune players

The study found that within the TLSs, certain types of immune cells are very active:

  • T cells: These include various types, some of which help other immune cells, while others can cause inflammation and tissue damage. Some T cells in HS produce substances called IL-17A and IFNG, which contribute to the problem. There are also regulatory T cells (Tregs) that normally suppress the immune system, but in HS they may not work properly or can also produce IL-17A, which is unusual.
  • B cells and plasma cells: These cells make antibodies. In HS, there is a big increase in these cells, particularly plasma cells, which produce antibodies that attack the patient’s own skin cells (keratinocytes). These antibodies are found in the skin lesions themselves, and they are thought to contribute to the inflammation and tissue damage seen in HS.

The role of fibroblasts

Fibroblasts, which are cells that support and help form tissues, also play a key role in HS. In HS, certain fibroblasts produce chemicals called CXCL13 and CCL19. These chemicals act like a signal to attract immune cells and cause them to gather into aggregates. This is part of a feedback loop; when immune cells are activated, they release substances like TNF-alpha, which in turn stimulates fibroblasts to produce more CXCL13 and CCL19.

How this impacts treatment

These new discoveries have important implications for how HS is treated. Current treatments like TNF-alpha blockers can be helpful, but they don't work for everyone. The research shows that TNF-alpha is critical for starting the process of lymphocyte aggregation, but once the aggregates form, blocking TNF-alpha doesn't work as well. This suggests we might need to explore new ways to interrupt these feedback loops and stop TLS formation.

The study also supports the idea that HS is an autoimmune condition, where the body’s immune system is mistakenly attacking its own tissues. This information helps to direct future research to better understand the autoantigens that trigger this process, so treatments can be tailored to specifically target the underlying causes of HS.

In conclusion

This research provides valuable insights into the complex mechanisms driving HS. It highlights the importance of TLSs, the specific immune cells involved, and the role of fibroblasts in perpetuating the disease. By understanding these processes, we can develop more effective treatments to reduce inflammation, prevent tissue damage, and improve the quality of life for people living with HS. The discovery that skin fibroblasts from specific body regions can upregulate CXCL13 and CCL19 expression in response to inflammation also points to the regional specificity of the condition and the potential for targeted treatments. Further research should aim to identify the autoantigen that stimulates the production of autoantibodies.

Journal information: Skin immune-mesenchymal interplay within tertiary lymphoid structures promotes autoimmune pathogenesis in hidradenitis suppurativa. Immunity (2024).  10.1016/j.immuni.2024.11.010

Additional information: https://www.cell.com/immunity/home


Location: Oxford, UK

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