Research Topic

The Role of Natural Killer Cells in Autoimmune Diseases

About this Research Topic

The innate immune system represents the first line of defense in the protection of the host from the attack from infectious agents and the prevention of tumor development. Its functional activity is complementary to that of the adaptive immune system, which in concert with it confers the necessary protection from immune-mediated diseases. This allows immune homeostasis to maintain effective immune responses while avoiding self-tissue damage. However, impairment or a dysregulation of the otherwise normally operating mechanisms of immune tolerance can lead to aberrant immune responses and subsequent development of autoimmune diseases. NK cells are key components of the innate immune system. In addition to their most evident role of host protection from virally-infected and transformed cells, NK cells have also been shown to participate in the control of autoimmune diseases, directly or indirectly.

The pathogenesis of autoimmune diseases is multifactorial, however, still remains to be fully clarified. Autoimmune conditions are principally due to B and T lymphocyte responses. However, NK cells have also been recognized to play a role in the promotion and/or maintenance of altered adaptive immune responses. NK cells are involved in the establishment of peripheral tolerance and immune regulation in preventing autoimmune disorder onset. This occurs through the cross-talk of NK cells with DCs and T cells via different receptor-ligand pairs. In addition, with the loss of HLA-I immune responses involving NK cells directed towards self-antigens can occur.

Despite NK cells having not been distinguished from NK T cells by initial studies, several recent investigations have demonstrated altered NK cell numbers both in the peripheral blood and affected tissues of patients with autoimmune conditions. Furthermore, altered NK cell function, such as a defective cytotoxic activity was observed in several autoimmune disorders. More specifically, a correlation has been observed with Type 1 diabetes, rheumatoid arthritis, systemic-onset juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, inflammatory bowel disease, multiple sclerosis, and Behcet's disease. It is plausible that the reduction in peripheral blood NK cells reported in autoimmune patients could be related to their trafficking to damaged tissues. Additionally, NK cells can behave differently in the development of autoimmune disorders, they can either promote disease onset or have a protective effect against the disease. A better understanding of the mechanisms by which NK cells can modulate autoimmune disease could have relevant implications for the design of new strategies of targeted therapeutic immune intervention.

This Research Topic aims at providing an overview and focused discussions on the recent discoveries and investigations that are defining how NK cells can influence the initiation, progression, and outcomes of several autoimmune diseases. We welcome authors to submit Original Research, Review and Perspective articles focusing on, but not limited to, the following subtopics:

1. The role of NK cells in the etiopathogenesis of autoimmune diseases
2. Studies in animal models of the role of NK cells in autoimmune diseases
3. Human studies on the role of NK cells in autoimmunity
4. Perspectives on future therapeutic approaches targeting NK cells


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The innate immune system represents the first line of defense in the protection of the host from the attack from infectious agents and the prevention of tumor development. Its functional activity is complementary to that of the adaptive immune system, which in concert with it confers the necessary protection from immune-mediated diseases. This allows immune homeostasis to maintain effective immune responses while avoiding self-tissue damage. However, impairment or a dysregulation of the otherwise normally operating mechanisms of immune tolerance can lead to aberrant immune responses and subsequent development of autoimmune diseases. NK cells are key components of the innate immune system. In addition to their most evident role of host protection from virally-infected and transformed cells, NK cells have also been shown to participate in the control of autoimmune diseases, directly or indirectly.

The pathogenesis of autoimmune diseases is multifactorial, however, still remains to be fully clarified. Autoimmune conditions are principally due to B and T lymphocyte responses. However, NK cells have also been recognized to play a role in the promotion and/or maintenance of altered adaptive immune responses. NK cells are involved in the establishment of peripheral tolerance and immune regulation in preventing autoimmune disorder onset. This occurs through the cross-talk of NK cells with DCs and T cells via different receptor-ligand pairs. In addition, with the loss of HLA-I immune responses involving NK cells directed towards self-antigens can occur.

Despite NK cells having not been distinguished from NK T cells by initial studies, several recent investigations have demonstrated altered NK cell numbers both in the peripheral blood and affected tissues of patients with autoimmune conditions. Furthermore, altered NK cell function, such as a defective cytotoxic activity was observed in several autoimmune disorders. More specifically, a correlation has been observed with Type 1 diabetes, rheumatoid arthritis, systemic-onset juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, inflammatory bowel disease, multiple sclerosis, and Behcet's disease. It is plausible that the reduction in peripheral blood NK cells reported in autoimmune patients could be related to their trafficking to damaged tissues. Additionally, NK cells can behave differently in the development of autoimmune disorders, they can either promote disease onset or have a protective effect against the disease. A better understanding of the mechanisms by which NK cells can modulate autoimmune disease could have relevant implications for the design of new strategies of targeted therapeutic immune intervention.

This Research Topic aims at providing an overview and focused discussions on the recent discoveries and investigations that are defining how NK cells can influence the initiation, progression, and outcomes of several autoimmune diseases. We welcome authors to submit Original Research, Review and Perspective articles focusing on, but not limited to, the following subtopics:

1. The role of NK cells in the etiopathogenesis of autoimmune diseases
2. Studies in animal models of the role of NK cells in autoimmune diseases
3. Human studies on the role of NK cells in autoimmunity
4. Perspectives on future therapeutic approaches targeting NK cells


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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