Immunosuppressive roles of natural killer T (NKT) cells in the skin

McKee, Sara; Mattarollo, Stephen R.; Leggatt, Graham R.

doi:10.1189/jlb.4ru0114-001r

Cited by 18 publications

(10 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, NKT cells can suppress immune responses during various conditions such as cancer or UV-induced photo damage. Conversely, NKT cells are also able to activate immune responses, such as in psoriasis and liver inflammation272829. In this paper we demonstrate that other T cell subclasses are not involved in the effector phase of our animal model of EBA.…”

Section: Discussionmentioning

confidence: 64%

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Bieber

Witte

Sun

et al. 2016

Sci Rep

View full text Add to dashboard Cite

T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organspecific autoimmune disease, namely epidermolysis bullosa acquisita ( T cells are essential regulators of host defense and exhibit direct cytotoxic as well as regulatory properties. The presence or absence of pro-inflammatory compared with regulatory T cell subsets affects the development and outcome of inflammatory reactions. Misbalance of T cell populations leads to autoimmune disorders, including systemic lupus erythematosus (SLE), different autoimmune bullous dermatoses (AIBDs) and rheumatoid arthritis (RA) [1][2][3] . In these diseases, the contribution of T cells to antibody production and maintenance of the autoimmune response has clearly been demonstrated 4,5 . In recent decades, the understanding of autoantibody-induced tissue injury has greatly improved. However, the role of T cells during the effector phase of autoimmune skin blistering diseases, i.e., tissue injury and inflammation in the targeted organs, is not completely understood. In this study, we investigated the role of T cells during this phase, using a mouse model of epidermolysis bullosa acquisita (EBA), a prototypical organ-specific autoimmune disease 6,7 . EBA is caused by autoantibodies directed against type VII collagen (COL7), an integral component of anchoring fibrils 8 . Animal models, employing antibody transfer into mice 9,10 , have added to a greater understanding of the mechanisms leading to blistering in EBA 9,11,12 . Based on the current understanding of EBA pathogenesis, the effector phase of EBA is predominantly driven by neutrophils -their depletion leading to a complete absence of experimental EBA 13. With regard to T cell involvement during this phase, in vivo and in vitro data have been contradictory. In vivo data indicated a T cell-independent process: Transfer of total IgG isolated from rabbits that had been immunized with COL7 into T cell-deficient mice induced subepidermal blistering 9 . However, in that study, no wild-type control for evaluation of the extent of blistering was included. In other

show abstract

Section: Discussionmentioning

confidence: 64%

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Bieber

Witte

Sun

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The dermis is home to a diverse array of specialized immune cells including antigen-presenting dermal DCs, T cells, B cells, and natural killer (NK) cells, as well as mast cells, monocytes, and macrophages [2,4,5]. The contribution of different immune cell components to cutaneous immune responses has been thoroughly investigated in recent years [5][6][7][8][9], and these efforts have led to significant advances in the treatment of inflammatory skin conditions and skin tumors, including the use of immunobiological agents developed as a result of an improved understanding of the cutaneous immune system. Of particular note, recent developments in the treatment of metastatic melanoma aimed at stimulating the antitumor immune response have offered improved survival for patients where therapeutic options were previously very limited [10].…”

mentioning

confidence: 99%

Revisiting the role of B cells in skin immune surveillance

Egbuniwe

Karagiannis

Nestle

et al. 2015

Trends in Immunology

View full text Add to dashboard Cite

Whereas our understanding of the skin immune system has increased exponentially in recent years, the role of B cells in cutaneous immunity remains poorly defined. Recent studies have revealed the presence of B cells within lymphocytic infiltrates in chronic inflammatory skin diseases and cutaneous malignancies including melanoma, and have examined their functional significance in these settings. We review these findings and discuss them in the context of the current understanding of the role of B cells in normal skin physiology, as well as in both animal and human models of skin pathology. We integrate these findings into a model of cutaneous immunity wherein crosstalk between B cells and other skin-resident immune cells plays a central role in skin immune homeostasis.

show abstract

“…This may be due to a strong, local activation of skin NKT cells, which can promote or inhibit adaptive immune responses (37). However, a suppressive role for NKT cells in allergic reactions has been described (38,39). The recruitment and activation of resident and peripheral APCs, respectively, may also amplify the local immune response (34,40).…”

Section: Discussionmentioning

confidence: 99%

Antileishmanial Effects of Synthetic Eh PIb Analogs Derived from the Entamoeba histolytica Lipopeptidephosphoglycan

Fehling

Choy

Ting

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

With an estimated number of new cases annually of approximately 1.4 million, leishmaniasis belongs to the most important parasitic diseases in the world. Nevertheless, existing drugs against leishmaniasis in general have several drawbacks that urgently necessitate new drug development. A glycolipid molecule of the intestinal protozoan parasite Entamoeba histolytica and its synthetic analogs previously showed considerable immunotherapeutic effects against Leishmania major infection. Here, we designed and synthesized a series of new immunostimulatory compounds derived from the phosphatidylinositol b anchor of Entamoeba histolytica (EhPIb) subunit of the native compound and investigated their antileishmanial activity in vitro and in vivo in a murine model of cutaneous leishmaniasis. The new synthetic EhPIb analogs showed almost no toxicity in vitro. Treatment with the analogs significantly decreased the parasite load in murine and human macrophages in vitro. In addition, topical application of the EhPIb analog Eh-1 significantly reduced cutaneous lesions in the murine model, correlating with an increase in the production of selected Th1 cytokines. In addition, we could show in in vitro experiments that treatment with Eh-1 led to a decrease in mRNA expression of arginase-1 (Arg1) and interleukin 4 (IL-4), which are required by the parasites to circumvent their elimination by the immune response. The use of the host-targeting synthetic EhPIb compounds, either alone or in combination therapy with antiparasitic drugs, shows promise for treating cutaneous leishmaniasis and therefore might improve the current unsatisfactory status of chemotherapy against this infectious disease.

show abstract

Immunosuppressive roles of natural killer T (NKT) cells in the skin

Cited by 18 publications

References 83 publications

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Revisiting the role of B cells in skin immune surveillance

Antileishmanial Effects of Synthetic Eh PIb Analogs Derived from the Entamoeba histolytica Lipopeptidephosphoglycan

Contact Info

Product

Resources

About