Type 2 immunity plays an essential role for murine model of allergic contact dermatitis with mixed type 1/type 2 immune response

Objective:We postulated that either oral or vaginal administration of the immune response modifier imiquimod would decrease vaginal shedding ofChlamydia trachomatis, mouse pneumonitis strain (MoPn), in a murine model.Methods:Female BALB/c mice were infected intravaginally withC. trachomatis(MoPn) and were administered imiquimod either orally (30 mg/kg) or vaginally (10 μl of 5%imiquimod cream) prior to infection and every second day after infection for a total of four doses. The course of infection was monitored by collecting cervical–vaginal swabs and isolation in HeLa 229 cell culture. To determine whether the drug affected T helper type 1 or T helper type 2 immune response polarization, immunoglobulinG(IgG) subclass antibody responses were assessed at day 56 after infection.Results:There was no significant difference in the course of infection when imiquimod-treated mice were compared with sham-treated controls, regardless of whether the drug was administered orally or vaginally. IgG subclass antibody responses, and by extension, T helper type 1 to T helper type 2 immune response polarization, were also unaffected.Conclusions:Imiquimod has no efficacy in controllingC. trachomatis(MoPn) infection in the murine model.

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Blocking type 2 inflammation by dupilumab does not control classic (type 1‐driven) allergic contact dermatitis in chronic hand eczema

Contact Dermatitis ◽

10.1111/cod.13266 ◽

2019 ◽

Vol 81 (2) ◽

pp. 145-147 ◽

Cited By ~ 5

Author(s):

Marie‐Noëlle Crepy ◽

Audrey Nosbaum ◽

Lynda Bensefa‐Colas

Keyword(s):

Contact Dermatitis ◽

Allergic Contact Dermatitis ◽

Hand Eczema ◽

Chronic Hand Eczema ◽

Allergic Contact ◽

Type 2 Inflammation ◽

Blocking Type

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The role of dupilumab in managing allergic contact dermatitis

SKIN The Journal of Cutaneous Medicine ◽

10.25251/skin.3.4.1 ◽

2019 ◽

Vol 3 (4) ◽

pp. 234-238

Author(s):

Andrew Desrosiers ◽

Thy Huynh ◽

Stephen Helms ◽

Robert Brodell

Keyword(s):

Contact Dermatitis ◽

Allergic Contact Dermatitis ◽

Limited Evidence ◽

Immunological Responses ◽

Type 2 Immune Response ◽

Allergic Contact ◽

The Cost ◽

Systemic Therapies

Recently, there has been vigorous debate about the value of using dupilumab, a biologic that targets TH2-mediated processes, in the management of recalcitrant allergic contact dermatitis. A review of the current literature found the following: 1) The cytokine polarity of the immunologic response in ACD depends upon the inciting allergen, so the therapeutic approach to ACD must be individualized; 2) a single allergen can elicit different immunological responses in patients with and without underlying AD; 3) there is limited evidence in support of using dupilumab for ACD in patients without concomitant AD; 4) the cost of this drug further argues against its use in all patients with ACD; 5) dupilumab’s benign side effect profile, particularly its lack of immunosuppression, relative to other systemic therapies make it a reasonable option in AD patients with systemic ACD to certain allergens known to elicit a significant type 2 immune response who have failed other treatments.

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Cl− channel is required for CXCL10-induced neuronal activation and itch response in a murine model of allergic contact dermatitis

Journal of Neurophysiology ◽

10.1152/jn.00187.2017 ◽

2017 ◽

Vol 118 (1) ◽

pp. 619-624 ◽

Cited By ~ 9

Author(s):

Lintao Qu ◽

Kai Fu ◽

Steven G. Shimada ◽

Robert H. LaMotte

Keyword(s):

Contact Dermatitis ◽

Allergic Contact Dermatitis ◽

Murine Model ◽

Behavioral Effects ◽

Contact Hypersensitivity ◽

Squaric Acid ◽

Neuronal Activation ◽

Ionic Mechanisms ◽

Cxcr3 Signaling ◽

Allergic Contact

Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS. This current was modulated by intracellular Cl− and blocked by the general Cl− channel inhibitors. Moreover, increasing Ca2+ buffering capacity reduced this current. In addition, blockade of Cl− channels significantly suppressed CXCL10-induced Ca2+ response. In behavioral tests, injection of CXCL10 into CHS site exacerbated itch-related scratching behaviors. Moreover, the potentiating behavioral effects of CXCL10 were attenuated by either of two Cl− channel blockers. Thus we suggest that the Cl− channel acts as a downstream target mediating the excitatory and pruritic behavioral effects of CXCL10. Cl− channels may provide a promising therapeutic target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate. NEW & NOTEWORTHY The ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch are largely unexplored. This study revealed that CXCL10 evoked an ionic current mainly carried by Cl− channels. We suggest that Cl− channels are likely key molecular candidates responsible for the CXCL10-evoked neuronal activation and itch-like behaviors in a murine model of allergic contact dermatitis induced by the antigen squaric acid dibutylester. Cl− channels may emerge as a promising drug target for the treatment of allergic itch in which CXCL10/CXCR3 signaling may participate.

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