On the Role of Co-inhibitory Molecules in Dendritic Cell: T Helper Cell Coculture Assays Aimed to Detect Chemical-Induced Contact Allergy

Abstract Chemokine CC motif receptor-like 2 (CCRL2) is a heptahelic transmembrane receptor that shows the highest degree of homology with CCR1, an inflammatory chemokine receptor. CCRL2 mRNA was rapidly (30 minutes) and transiently (2-4 hours) regulated during dendritic cell (DC) maturation. Protein expression paralleled RNA regulation. In vivo, CCRL2 was expressed by activated DC and macrophages, but not by eosinophils and T cells. CCRL2−/− mice showed normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T helper cell 2 response. CCRL2−/− mice were protected in a model of ovalbumin-induced airway inflammation, with reduced leukocyte recruitment in the BAL (eosinophils and mononuclear cells) and reduced production of the T helper cell 2 cytokines, interleukin-4 and -5, and chemokines CCL11 and CCL17. The central role of CCRL2 deficiency in DC was supported by the fact that adoptive transfer of CCRL2−/− antigen-loaded DC in wild-type animals recapitulated the phenotype observed in knockout mice. These data show a nonredundant role of CCRL2 in lung DC trafficking and propose a role for this receptor in the control of excessive airway inflammatory responses.

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Different T helper cell subsets elicited in mice utilizing two different adjuvant vehicles: The role of endogenous interleukin 1 in proliferative responses

Cellular Immunology ◽

10.1016/0008-8749(89)90011-7 ◽

1989 ◽

Vol 121 (1) ◽

pp. 134-145 ◽

Cited By ~ 192

Author(s):

James L. Grun ◽

Paul H. Maurer

Keyword(s):

Interleukin 1 ◽

T Helper Cell ◽

Helper Cell ◽

T Helper

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Folate deficiency affects dendritic cell function and subsequent T helper cell differentiation

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2016.11.008 ◽

2017 ◽

Vol 41 ◽

pp. 65-72 ◽

Cited By ~ 15

Author(s):

Chi-Heng Wu ◽

Tzu-Chien Huang ◽

Bi-Fong Lin

Keyword(s):

Cell Differentiation ◽

Dendritic Cell ◽

Cell Function ◽

Folate Deficiency ◽

T Helper Cell ◽

Helper Cell ◽

Dendritic Cell Function ◽

T Helper

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Crucial Role of the Interleukin 1 Receptor Family Member T1/St2 in T Helper Cell Type 2–Mediated Lung Mucosal Immune Responses

Journal of Experimental Medicine ◽

10.1084/jem.190.7.895 ◽

1999 ◽

Vol 190 (7) ◽

pp. 895-902 ◽

Cited By ~ 280

Author(s):

Anthony J. Coyle ◽

Clare Lloyd ◽

Jane Tian ◽

Trang Nguyen ◽

Christina Erikkson ◽

...

Keyword(s):

Immune Responses ◽

T Helper Cell ◽

Helper Cell ◽

Eosinophil Infiltration ◽

Cell Type ◽

T Helper ◽

Helper Cell Type ◽

Mucosal Immune Responses

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.

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