Immunophenotyping in pemphigus reveals a TH17/TFH17 cell–dominated immune response promoting desmoglein1/3-specific autoantibody production

Holstein, Julia; Solimani, Farzan; Baum, Carolin; Meier, Katharina; Pollmann, Robert; Didona, Dario; Tekath, Tobias; Dugas, Martin; Casadei, Nicolas; Hudemann, Christoph; Polakova, Alexandra; Matthes, Jakob; Schäfer, Iris; Yazdi, Amir S.; Eming, Rüdiger; Hertl, Michael; Pfützner, Wolfgang; Möbs, Christian

doi:10.1016/j.jaci.2020.11.008

Cited by 55 publications

(56 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serological data in humans support the role of Dsg 3‐reactive Th2 cells in stimulating B‐cell secretion of autoantibodies in PV 25 . Another population of interest is represented by the Tfh cells, which are increased in pemphigus patients and may thus play a role in the generation of autoantibodies by B cells 26,41 . Our characterization of Th cell and Tfh cell responses in pemphigus showed some differences in the frequency of subsets, especially in active patients.…”

Section: Discussionmentioning

confidence: 51%

“…Another interesting finding is represented by the expansion of Th17 and Tfh17 cells in pemphigus patients 26 . MDSCs have been implied in the generation of Th17 from naïve CD4 + T cells 48 .…”

Section: Discussionmentioning

confidence: 99%

“…Th cells were characterized as CD3 + , CD4 + , CD45RA − and CXCR5 − , while Tfh cells were defined as CD3 + , CD4 + , CD45RA − and CXCR5 + . The different Th and Tfh subsets were characterized as following: Th1 or Tfh1 cells: CXCR3 + , CCR6 − ; Th2 or Tfh2 cells: CXCR3 − , CCR6 − ; Th17 or Tfh17 cells: CXCR3 − , CCR6 + ; T regulatory (Treg) or T follicular regulatory (Tfreg) cells: CD25 +/high , CD117 −/low 26,35,36 (as depicted in Figure 3A).…”

Section: Methodsmentioning

confidence: 99%

“…According to recent studies, the production of Dsg‐specific autoantibodies by B cells is driven by Dsg‐specific autoreactive Th and T follicular helper (Tfh) cells 25,26 . Interleukin‐4 (IL‐4) producing Dsg autoreactive Th2 cells have been described in acute and chronic patients, while Interferon gamma (IFNγ) producing Th1 cells seem to be predominant in remitting patients 27,28 .…”

Section: Introductionmentioning

confidence: 99%

“…A dysfunction in IL‐10 secreting Treg cells might also be implied in the loss of tolerance against Dsgs 29 . More recent studies also suggest an Important role of Th17 and Tfh cell populations in pemphigus pathogenesis 26,30–32 …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Neri

Carevic-Neri

Brück

et al. 2021

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which are characterized by their capability to suppress T‐cell responses. While MDSCs have been traditionally associated with cancer diseases, their role as regulators of autoimmune diseases is emerging. Pemphigus is a chronic autoimmune blistering skin disease characterized by dysregulated T‐cell responses and autoantibody production. The role of MDSCs in pemphigus disease has not been defined yet. The aim of this study was to characterize MDSCs in pemphigus patients and to dissect their relationship with CD4+ T‐cell subsets and clinical disease assessments. For this purpose, we performed a cross‐sectional analysis of 20 patients with pemphigus. Our results indicate that a population of CD66b+CD11b+ polymorphonuclear‐like MDSCs (PMN‐MDSCs) is expanded in the peripheral blood mononuclear cell fraction of pemphigus patients compared to age‐matched healthy donors. These PMN‐MDSCs have the capability of suppressing allogeneic T‐cell proliferation in vitro and show increased expression of characteristic effector molecules such as arginase I and interleukin‐10. We further demonstrate that PMN‐MDSCs are especially expanded in patients with active pemphigus, but not in patients in remission. Moreover, MDSC frequencies correlate with an increased Th2/Th1 cell ratio. In conclusion, the identification of a functional PMN‐MDSC population suggests a possible role of these cells as regulators of Th cell responses in pemphigus.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Neri

Carevic-Neri

Brück

et al. 2021

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

Interleukin‐21 in autoimmune and inflammatory skin diseases

et al. 2023

Self Cite

View full text Add to dashboard Cite

Studies on the role of interleukins (ILs) in autoimmune and inflammatory diseases allow for the better understanding of pathologic mechanisms of disease and reshaping of treatment modalities. The development of monoclonal antibodies targeting specific ILs or IL signaling pathways (i.e., anti‐IL‐17/IL‐23 in psoriasis or anti‐IL‐4/IL‐13 in atopic dermatitis) is the shining example of therapeutic interventions in research. IL‐21, belonging to the group of ɣc‐cytokines (IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15), is gaining attention for its pleiotropic role in several types of immune cells as activator of various inflammatory pathways. In both health and disease, IL‐21 sustains T‐ and B‐cell activity. Together with IL‐6, IL‐21 helps to generate Th17 cells, promotes CXCR5 expression in T cells, and their maturation into follicular T helper cells. In B cells, IL‐21 sustains their proliferation and maturation into plasma cells and promotes class switching and antigen‐specific antibody production. Due to these characteristics, IL‐21 is a main factor in numerous immunologic disorders, such as rheumatoid arthritis and MS. Studies in preclinical skin disease models and on human skin strongly suggest that IL‐21 is crucially involved in inflammatory and autoimmune cutaneous disorders. Here, we summarize the current knowledge of IL‐21 in well‐known skin diseases.

show abstract

Pemphigus: current and future treatment strategies

Kussini,

Kaisers,

Sequeira Santos

et al. 2023

Dermatologie

View full text Add to dashboard Cite

Immunophenotyping in pemphigus reveals a TH17/TFH17 cell–dominated immune response promoting desmoglein1/3-specific autoantibody production

Cited by 55 publications

References 67 publications

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Interleukin‐21 in autoimmune and inflammatory skin diseases

Pemphigus: current and future treatment strategies

Contact Info

Product

Resources

About

Immunophenotyping in pemphigus reveals a TH17/TFH17 cell–dominated immune response promoting desmoglein1/3-specific autoantibody production

Cited by 55 publications

References 67 publications

Arginase 1+ IL‐10+ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Arginase 1+ IL‐10+ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Interleukin‐21 in autoimmune and inflammatory skin diseases

Pemphigus: current and future treatment strategies

Contact Info

Product

Resources

About

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response

Arginase 1⁺ IL‐10⁺ polymorphonuclear myeloid‐derived suppressor cells are elevated in patients with active pemphigus and correlate with an increased Th2/Th1 response