Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 May 29:10:1198.
doi: 10.3389/fimmu.2019.01198. eCollection 2019.

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Wolf-Henning Boehncke  1   2 , Nicolo Costantino Brembilla  1
Affiliations
Review

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Wolf-Henning Boehncke et al. Front Immunol. .

Abstract

The presence of one or several autoantigen(s) and a response by the adaptive immune system are the key criteria to classify a pathology as an autoimmune disease. The list of entities fulfilling this criterion is currently growing in the light of recent advancements in the pathogenetic understanding of a number of important dermatoses. The role of autoreactive T-lymphocytes differs amongst these pathologies. While they are directly involved as effector cells attacking and sometimes killing their respective target in some diseases (e.g., vitiligo), they provide help to B-lymphocytes, which in turn produce the pathogenic autoreactive antibodies in others (pemphigus and pemphigoid). Atopic dermatits is a chimera in this regard, as there is evidence for both functions. Psoriasis is an example for an entity where autoantigens were finally identified, suggesting that at least a subgroup of patients should be classified as suffering from a true autoimmune rather than autoinflammatory condition. Identification of resident memory T-lymphocytes (TRM) helped to understand why certain diseases relapse at the same site after seemingly effective therapy. Therefore, the in-depth characterization of autoreactive T-lyphocytes goes way beyond an academic exercise and opens the door toward improved therapies yielding durable responses. TRM are particularly suitable targets in this regard, and the clinical efficacy of some established and emerging therapeutic strategies such as the inhibition of Janus Kinase 3 or interleukin 15 may rely on their capacity to prevent TRM differentiation and maintenance. Research in this field brings us closer to the ultimate goal in the management of autoimmunity at large, namely resetting the immune system in order to restore the state of tolerance.

Keywords: alopecia areata; atopic dermatitis; bullous pemphigoid; pemphigus; psoriasis; resident memory T-lymphocytes; scleroderma; vitiligo.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Shaping the T-cell repertoire. T-lymphocytes undergo positive selection to ensure restriction to the host's antigen presenting molecules as well as negative selection to eliminate strongly autoreactive cells in the thymus prior to populating the periphery. T-cells whose TCR affinity is close to the threshold for negative selection have a high potential for autoreactivity and escape thymic negative selection. A subset of these cells is programmed to become Treg cells, others (the potentially pathogeneic autoreactive cells) are kept under the control of the peripheral tolerance.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Koehli S, Naeher D, Galati-Fournier V, Zehn D, Palmer E. Optimal T-cell receptor affinity for inducing autoimmunity. Proc Natl Acad Sci USA. (2014) 111:17248–53. 10.1073/pnas.1402724111 - DOI - PMC - PubMed
    1. Eldershaw SA, Sansom DM, Narendran P. Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue. Clin Exp Immunol. (2011) 163:296–308. 10.1111/j.1365-2249.2010.04316.x - DOI - PMC - PubMed
    1. Richards DM, Kyewski B, Feuerer M. Re-examining the nature and function of self-reactive T cells. Trends Immunol. (2016) 37:114–25. 10.1016/j.it.2015.12.005 - DOI - PMC - PubMed
    1. Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol. (2010) 11:21–7. 10.1038/ni.1817 - DOI - PubMed
    1. Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev. (2014) 259:88–102. 10.1111/imr.12160 - DOI - PMC - PubMed

Publication types