scholarly journals The Concept of Pathogenic TH2 Cells: Collegium Internationale Allergologicum Update 2021

2021 ◽  
Vol 182 (5) ◽  
pp. 365-380
Author(s):  
Nicole L. Bertschi ◽  
Cecilia Bazzini ◽  
Christoph Schlapbach

T helper (T<sub>H</sub>) cells have evolved into distinct subsets that mediate specific immune responses to protect the host against a myriad of infectious and noninfectious challenges. However, if dysregulated, T<sub>H</sub>-cell subsets can cause inflammatory disease. Emerging evidence now suggests that human allergic disease is caused by a distinct subpopulation of pathogenic T<sub>H</sub>2 cells. Pathogenic T<sub>H</sub>2 cells from different type-2-driven diseases share a core phenotype and show overlapping functional attributes. The unique differentiation requirements, activating signals, and metabolic characteristics of pathogenic T<sub>H</sub>2 cells are just being discovered. A better knowledge of this particular T<sub>H</sub>2 cell population will enable the specific targeting of disease-driving pathways in allergy. In this review, we introduce a rational for classifying T<sub>H</sub> cells into distinct subsets, discuss the current knowledge on pathogenic T<sub>H</sub>2 cells, and summarize their involvement in allergic diseases.

2020 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Riccardo Guidi ◽  
Christopher J. Wedeles ◽  
Mark S. Wilson

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.


1999 ◽  
Vol 190 (7) ◽  
pp. 895-902 ◽  
Author(s):  
Anthony J. Coyle ◽  
Clare Lloyd ◽  
Jane Tian ◽  
Trang Nguyen ◽  
Christina Erikkson ◽  
...  

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.


PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192541 ◽  
Author(s):  
Limei Shen ◽  
Stefan Tenzer ◽  
Moritz Hess ◽  
Ute Distler ◽  
Ingrid Tubbe ◽  
...  

2001 ◽  
Vol 193 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Hiroyuki Hirai ◽  
Kazuya Tanaka ◽  
Osamu Yoshie ◽  
Kazuyuki Ogawa ◽  
Kazumi Kenmotsu ◽  
...  

Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells in a Gαi-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.


1998 ◽  
Vol 27 (2-3) ◽  
pp. 50-58 ◽  
Author(s):  
Jonathan L Heeney ◽  
Mariëlle E. Gils ◽  
Peter Meide ◽  
Carlo de Giuli Morghen ◽  
Cristina Ghioni ◽  
...  

2009 ◽  
Vol 32 (4) ◽  
pp. 760-763 ◽  
Author(s):  
Yumi Inoue ◽  
Noriyuki Iwabuchi ◽  
Jin-zhong Xiao ◽  
Tomoko Yaeshima ◽  
Keiji Iwatsuki

Author(s):  
Vera A. Reviakina ◽  
Natalia A. Geppe ◽  
Aleksandr B. Malakhov ◽  
Oleg V. Kaliuzhin ◽  
Natalia G. Astaf'eva ◽  
...  

Significant progress has been made over the past decade in the treatment of allergic diseases such as atopic dermatitis and bronchial asthma. Dupilumab, which targets interleukin IL-4 and IL-13, has become an innovative targeted therapy. Immunobiologic therapy with the interleukin inhibitor is indicated for patients with moderate to severe uncontrolled atopic dermatitis, moderate to severe eosinophilic phenotype of uncontrolled Bronchial asthma and patients with poorly controlled severe chronic polyposis rhinosinusitis. A clinical case and recent data on the use of dupilumab for the treatment of type 2 inflammatory disease and prospects for its use are discussed.


1992 ◽  
Vol 4 (6) ◽  
pp. 788-793 ◽  
Author(s):  
Martien L. Kapsenberg ◽  
Henk M. Jansen ◽  
Jan D. Bos ◽  
Eddy A. Wierenga

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