New Evidence that Th17 Cells Contribute to Hashimoto’s Thyroiditis

New Evidence that Th17 Cells Contribute to Hashimoto’s Thyroiditis

Commentary

On the study
by K Degertekin et al, Cytokine, 2016, 80:13-7
Circulating Th17 cytokine levels are altered in Hashimoto’s thyroiditis

The T helper (Th)1/Th2 paradigm has been used to explain many aspects of immune physiology and several immune-associated pathological conditions. Recent progress in the field has prompted increased focus on other effector T lymphocytes such as Th17 cells, central players in immune homeostasis and inflammatory processes (1). Th17 cells not only act against extracellular microbes through neutrophil recruitment to sites of infection, but they are also involved in the maintenance of normal intestinal and skin epithelial function and the protection from bowel infections (2).

Recent evidence implicating Th17 cells in the development and progression of immune/inflammatory disorders has helped to explain the pathogenic processes in psoriasis, rheumatoid arthritis, inflammatory bowel disease, celiac disease, systemic lupus erythematosus, multiple sclerosis and many other conditions (1-3). As a result, new therapeutic strategies targeting Th17 pathways have been developed (4).

However, the involvement of Th17 cells in thyroid autoimmune diseases remains poorly understood. The authors focused their work on Hashimoto’s thyroiditis (HT), as this is the most common autoimmune thyroid disease at any age (5) and which onset has long been thought to be Th1 cell-mediated only. The study investigates circulating Th17 cytokine (IL-17 and IL-23) levels in Hashimoto’s thyroiditis patients.

Of note, both hypothyroid and euthyroid HT patients are included in the study. Serum IL-17 and IL-23 levels were significantly higher in euthyroid HT individuals than in hypothyroid HT subjects and in the control group. While other studies support the importance of Th17 cells for HT pathogenesis, thyroid hormone status of the HT patients is typically not specified. The increased peripheral IL-17 and IL-23 levels noted in the context of euthyroidism suggests, for the first time, a more pivotal involvement of Th17 cells in an initial stage of the disease, as compared to the later phase when hypothyroidism is manifested.

The presence of bidirectional immune-endocrine interactions is well-known. An increase of circulating thyroid hormone levels in mice has been reported few days after alloimmunization, before the development of evident humoral and cellular responses (6). Therefore, it is highly likely that at earlier stages of the disease the rise in thyroid hormone levels is triggered by the Th17 cell activation. In this context, the normal values of FT4 or FT3, displayed by HT euthyroid group and some subjects admitted to the HT hypothyroid group, might respond, at least in part, to the increase of IL-17 and IL-23 at early stages of the disease. This could count as an additional effect that contributes to thyroid status apart from the gland tissue injury itself.

Also, the authors suggest that the Th17 system could have different functions at different stages of HT, leading to local inflammation and stromal fibrosis, at first, and then switching to a Th1 response, which would be most involved in HT of a more aggressive kind. Finally, they try to find a correlation between the loss of healthy thyroid tissue and the cytokine fluctuations. However, they found no correlation between thyroid volumes evaluated by thyroid ultrasonography and the IL-17 or IL-23 circulating levels.

The authors conclude that the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. Better comprehension of the Th17 system involvement in thyroid autoimmune diseases is important for the development of new therapeutic strategies, as is understanding Th1, Th2, Th17, and Treg cytokine profiles at the tissue level. Also, it would be interesting to evaluate how activation of Th17 cells may be related to other autoimmune comorbidities, given autoimmune thyroiditis is associated with various other nonthyroid autoimmune conditions in patients of all ages, such as connective tissue diseases, type 1 diabetes, and celiac disease (5).

The study has some limitations, such as a small number of participants, but it provides some preliminary insight into the interplay between immune mediators and hormone levels in a common autoimmune disease, as well as raises new questions that deserve further investigation.

Authors Affiliation:

Alicia Juana Klecha, PhD – Laboratorio de Radioisótopos-Cátedra de Física. Facultad de Farmacia y Bioquímica. Universidad Nacional de Buenos Aires, and Department of Neuroimmunomodulation and Molecular Oncology, Institute for Biomedical Research (BIOMED), Catholic University of Argentina (UCA), National Research Council of Argentina (CONICET), Buenos Aries, Argentina; email: alijuk@yahoo.com

María Laura Barreiro Arcos, PhD – Department of Neuroimmunomodulation and Molecular Oncology, Institute for Biomedical Research (BIOMED), Catholic University of Argentina (UCA), National Research Council of Argentina (CONICET), Buenos Aries, Argentina; email: mlbarreiro@yahoo.com.ar

References:

  1. Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol. 2016 Apr;28(4):163-71. doi: 10.1093/intimm/dxw006.
  2. Rossi M, Bot A. The Th17 cell population and the immune homeostasis of the gastrointestinal tract. Int Rev Immunol. 2013 Oct-Dec;32(5-6):471-4. doi: 10.3109/08830185.2013.843983.
  3. Nagy G, Huszthy PC, Fossum E, Konttinen Y, Nakken B, Szodoray P. Selected Aspects in the Pathogenesis of Autoimmune Diseases. Mediators Inflamm. 2015; ID:351732. doi: 10.1155/2015/351732.
  4. Fasching P, Stradner M, Graninger W, Dejaco C, Fessler J. Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders. Molecules. 2017 Jan 14;22(1). pii: E134. doi: 10.3390/molecules22010134.
  5. Ruggeri RM, Trimarchi F, Giuffrida G, Certo R, Cama E, Campennì A, Alibrandi A, De Luca F4, Wasniewska M4. Autoimmune comorbidities in Hashimoto’s thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol. 2017 Feb;176(2):133-141.
  6. Klecha AJ1, Genaro AM, Lysionek AE, Caro RA, Coluccia AG, Cremaschi GA. Experimental evidence pointing to the bidirectional interaction between the immune system and the thyroid axis. Int J Immunopharmacol. 2000 Jul;22(7):491-500.

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Source: Cover Image: Collage, Th17 cells and thyroid gland; Thyroid: Temporary Vitals: Thyroid 2008; Authors: Eve and Bowie, Credit: http://www.eveandbowie.com/projects/vitals2.html

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