Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p = 0.018). TSLP and TARC/CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
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http://dx.doi.org/10.4049/jimmunol.174.12.8183 | DOI Listing |
Stem Cells
January 2025
Sangamo Therapeutics, 501 Canal Blvd. Richmond, CA.
iPSCs can serve as a renewable source of a consistent edited cell product, overcoming limitations of primary cells. While feeder-free generation of clinical grade iPSC-derived CD8 T cells has been achieved, differentiation of iPSC-derived CD4sp and regulatory T cells requires mouse stromal cells in an artificial thymic organoid. Here we report a serum- and feeder-free differentiation process suitable for large-scale production.
View Article and Find Full Text PDFExpert Opin Emerg Drugs
January 2025
Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro - Catanzaro, Italy.
Introduction: Severe asthma is a chronic airway disease characterized by many pathomechanisms known as endotypes. Biological therapies targeting severe asthma endotypes have significantly improved the treatment of this disease, thus remarkably bettering patient quality of life.
Areas Covered: This review aims to describe current biological therapies for severe asthma, highlighting emerging ones.
Front Immunol
January 2025
Department of Pain Management, The State Key Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Background: The nod-like receptor family pyrin domain-containing 3 (NLRP3) has been implicated in various skin diseases. However, its role in mediating 2, 4-dinitrofluorobenzene (DNFB)-induced chronic itch remains unclear.
Methods: Widetype () and deletion ( )mice, the expression of transient receptor potential (TRP) ankyrin 1 (TRPA1) inhibitor or recombinant mice interleukin-18 (IL-18) were used to establish and evaluate the severity of DNFB-mediated chronic itch.
Int J Mol Sci
January 2025
Department of Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland.
Mastocytosis is a rare neoplastic disease of the bone marrow. Common symptoms like urticaria, diarrhea, bronchspasm and flushing are caused by mast cell degranulation and are mostly based on mast cell mediator release and Th2 type inflammation that occurs frequently in these patients. Psychological disorders are more prevalent in patients with systemic mastocytosis, though little is known about the mechanism behind this.
View Article and Find Full Text PDFIn recent years, a global increase in allergy incidence following chemical exposure has been observed. While the process of skin sensitization is well characterized through the adverse outcome pathway (AOP) framework, the immunological mechanisms underlying respiratory sensitization remain less well understood. Respiratory sensitizers are classified as substances of very high concern (SVHC) under the European Union (EU) regulation for the registration, evaluation, authorization and restriction of chemicals (REACH), emphasizing the importance of evaluating respiratory tract sensitization as a critical hazard.
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