In 1901, Paul Ehrlich conducted one of the landmark experiments in immunology. While studying the immune response in goats using blood from other animals, he observed that when blood from the same goat was used (in what we would now refer to as "autologous transfer"), no immune response was mounted. This observation led Ehrlich to propose the concept of ‘horror autotoxicus,’ suggesting it would be "dysteleological in the highest degree" to believe that an organism could mount an immune response against its own cells, as this would be profoundly maladaptive.

Forty years later, it was Frank Macfarlane Burnet who developed the concept of self-non-self, which became central to his subsequent “clonal selection theory” – a foundational paradigm in our understanding of adaptive immunity.

It is therefore not surprising that the study of autoimmunity has historically been focused on adaptive immunity, with early therapies targeting mainly this arm of the immune system: from calcineurin inhibitors to antimetabolites and B- and T-cell depleting monoclonal antibodies (such as Rituximab and Alemtuzumab).

Nevertheless, reports dating back to the mid-20th century have linked innate immune cells with both the development and the progression of autoimmune conditions. This idea was further supported by the clinical success of therapies targeting the innate immune pathways, such as anti-TNF biologics.

Recent studies have highlighted the roles of innate pathways in initiating immune responses against self, distinguishing self from non-self, and bridging the initial “insult” or breach of immune tolerance to adaptive immune activation In this research topic, we will focus on innate immune cells and their role in autoimmunity. We are particularly interested in macrophages, dendritic cells, neutrophils, and Innate Lymphoid Cells (ILCs). However, studies looking at other innate immune cells (e.g., eosinophils, mast cells) will also be considered.

We welcome contributions in the form of original research, review, mini review, case report, hypothesis and theory, perspective, both experimental and computational studies covering, but are not limited to, the following themes:

• Macrophages – including tissue-resident macrophages (such as microglia, kupffer cells, and alveolar macrophages) - in organ-specific autoimmunity.

• Neutrophil function and NETosis in both organ-specific and systemic
autoimmune conditions.

• NK-cells, as well as other ILCs at barrier organs, and their contribution to the breach of immune tolerance.

• Dendritic cells and their dual capacity to stimulate effector cells and to induce tolerance.

• Immune-stromal interactions involving innate immune cells in autoimmunity.

• Antigen Presentation in the context of autoimmune diseases.

Conflict of Interest: Prof. Pietro Invernizzi reports receiving research grant support from Gilead and Ipsen.

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Innate Immune Cells in Autoimmunity