Tacrolimus Improves the Implantation Rate in Patients with Elevated Th1/2 Helper Cell Ratio and Repeated Implantation Failure (RIF)

Abstract Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.

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Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model during Chlamydia muridarum genital infection

10.1101/863753 ◽

2019 ◽

Author(s):

Tesfaye Belay ◽

Elisha Martin ◽

Gezelle Brown ◽

Raenel Crenshaw ◽

Julia Street ◽

...

Keyword(s):

Mouse Model ◽

Genital Infection ◽

Th2 Cytokines ◽

T Helper ◽

T Helper 1 ◽

Chlamydia Muridarum ◽

T Helper 2 ◽

Induced Stress ◽

Ifn Γ ◽

Th1 And Th2

ABSTRACTA mouse model to study the effect of cold-induced stress on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Our previous results show that cold-induced stress increases the intensity of chlamydia genital infection, but little is known about the effect of cold-induced stress on differentiations and activities of T cell subpopulations and bone marrow derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines is not clear. The objective of this study was to examine whether cold-induced stress modulates the expression of transcription factors and hallmark cytokines of Th1 and Th2 or differentiation of BMDCs during C. muridarum genital infection in mice. Our results show that mRNA level of beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in mixed population of CD4+ T cells and BMDCs. Further, decreased expression of T-bet and low level of interferon-gamma (IFN-γ) production and increased expression of GATA-3 and interleukin-4 (IL-4) production in CD4+ T of stressed mice was observed. Exposure of BMDCs to feroterol (β2-AR agonist) or ICI,118551 (β2-AR antagonist), respectively, revealed significant stimulation or inhibition of β2-AR in stressed mice. Moreover, co-culturing of mature BMDC and naïve CD4+ T cells resulted in increased production of IL-4, IL-10, and IL-17 in culture supernatants, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that cold-induced stress is able to modulate the pattern of Th1 and Th2 cytokine environment, suggesting that it promotes the differentiation to Th2 rather than Th1 by the overexpression of GATA-3 correlated with elevated production of IL-4, IL-10, IL-23, and IL-17 in contrast to a low expression of T-bet correlated with less IFN-γ secretion in the mouse model.

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Changes in the T-helper 1 and 2 cell populations during pregnancy in tacrolimus-treated women with repeated implantation failure and recurrent pregnancy loss

Human Fertility ◽

10.1080/14647273.2021.1955415 ◽

2021 ◽

pp. 1-8

Author(s):

Michi Hisano ◽

Koji Nakagawa ◽

Joanne Kwak-Kim ◽

Rikikazu Sugiyama ◽

Haruhiko Sago ◽

...

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Cell Populations ◽

Implantation Failure ◽

T Helper ◽

T Helper 1 ◽

Repeated Implantation Failure

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Divergent Effects of Interleukin-4 and Interferon-γ on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses

Blood ◽

10.1182/blood.v92.8.2668.420k39_2668_2671 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2668-2671 ◽

Cited By ~ 2

Author(s):

Raffaella Bonecchi ◽

Silvano Sozzani ◽

Johnny T. Stine ◽

Walter Luini ◽

Giovanna D’Amico ◽

...

Keyword(s):

Constitutive Expression ◽

Interferon Γ ◽

Interleukin 4 ◽

Th2 Cells ◽

Mrna Levels ◽

T Helper ◽

T Helper 1 ◽

Chemokine Production ◽

T Helper 2 ◽

Ifn Γ

Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.

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Pengaruh Vaksinasi BCG Terhadap Serum Interferon Gamma pada Kasus Asma Ekstrinsik Atopi Anak

Sari Pediatri ◽

10.14238/sp10.3.2008.207-11 ◽

2016 ◽

Vol 10 (3) ◽

pp. 207

Author(s):

Yolanda Olivia Palandeng ◽

Diana Devi Takumansang Sondakh

Keyword(s):

Interferon Gamma ◽

Control Group ◽

T Helper ◽

T Helper 1 ◽

Control Group Design ◽

T Helper 2 ◽

Group Design ◽

Ifn Γ

Latar belakang. Prevalensi asma makin meningkat, diduga berkaitan dengan kejadian infeksi pada anak yang menurun sehingga menyebabkan pergeseran keseimbangan antara limfosit T helper 1 (Th1) dan T helper 2 (Th2) ke arah predominan Th2. Infeksi mikobakterium dan vaksinasi BCG dapat meningkatkan respon imun Th1 (interferon gamma (IFN-γ)) dan menekan Th2.Tujuan. Mengetahui pengaruh vaksinasi BCG terhadap kadar IFN-γ serum pasien asma ekstrinsik atopi anak setelah vaksinasi BCG satu kali.Metode. Penelitian kuasi-eksperimental pretest posttest control group design pada anak asma atopi. Pengacakan perlakuan dilakukan terhadap subjek ke dalam kelompok BCG dan plasebo. Sebelum dan 8 minggu sesudah perlakuan diukur kadar IFN-γ serum.Hasil. Kadar IFN-γ serum tidak meningkat sesudah vaksinasi BCG (median 1,580 dan 0,780 pg/ml, p= 0,326) dan plasebo (median 1,255 dan 0,670 pg/ml, p= 0,079). Selisih kadar IFN-γ serum kelompok BCG dan plasebo tidak berbeda bermakna (median 0,020 dan -0,420 pg/ml, p= 0,449).Kesimpulan. Kadar IFN-γ serum pasien asma ekstrinsik atopi anak tidak meningkat setelah vaksinasi BCG 1 kali.

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Divergent Effects of Interleukin-4 and Interferon-γ on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses

Blood ◽

10.1182/blood.v92.8.2668 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2668-2671 ◽

Cited By ~ 137

Author(s):

Raffaella Bonecchi ◽

Silvano Sozzani ◽

Johnny T. Stine ◽

Walter Luini ◽

Giovanna D’Amico ◽

...

Keyword(s):

Constitutive Expression ◽

Interferon Γ ◽

Interleukin 4 ◽

Th2 Cells ◽

Mrna Levels ◽

T Helper ◽

T Helper 1 ◽

Chemokine Production ◽

T Helper 2 ◽

Ifn Γ

Abstract Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper 1 (Th1) cells. The present study was designed to investigate the effect of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and interferon-γ (IFN-γ), on the production of MDC by human monocytes. IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and concentration-dependent (EC50 2 and 10 ng/mL, respectively) increase of MDC mRNA levels in monocytes. Increased expression of MDC mRNA was associated with protein release in the supernatant. MDC expression and production induced by IL-4 and IL-13 were inhibited by IFN-γ. IFN-γ also suppressed the constitutive expression of MDC in mature macrophages and dendritic cells. These results delineate an amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-γ and on the selectivity of this chemokine for polarized Th2 cells. © 1998 by The American Society of Hematology.

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Cumulative live birth rate after preimplantation genetic screening in repeated implantation failure: is there still a place for replacing genetically uncreened embryos?

10.26226/morressier.5912d9ead462b8029238629f ◽

2017 ◽

Author(s):

Marta Devesa Rodriguez de la Rua

Keyword(s):

Live Birth ◽

Genetic Screening ◽

Birth Rate ◽

Live Birth Rate ◽

Preimplantation Genetic Screening ◽

Implantation Failure ◽

Cumulative Live Birth Rate ◽

Repeated Implantation Failure ◽

Cumulative Live Birth

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OX40L–OX40 Signaling in Atopic Dermatitis

Journal of Clinical Medicine ◽

10.3390/jcm10122578 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2578

Author(s):

Masutaka Furue ◽

Mihoko Furue

Keyword(s):

T Cells ◽

Atopic Dermatitis ◽

Memory T Cells ◽

Effector Memory ◽

T Helper ◽

T Helper 1 ◽

Therapeutic Success ◽

T Helper 2 ◽

Promising Target ◽

Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

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Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis

Skin Appendage Disorders ◽

10.1159/000517832 ◽

2021 ◽

pp. 1-4

Author(s):

Maurizio Romagnuolo ◽

Mauro Barbareschi ◽

Simona Tavecchio ◽

Luisa Angileri ◽

Silvia Mariel Ferrucci

Keyword(s):

Atopic Dermatitis ◽

Skin Disorder ◽

Human Monoclonal Antibody ◽

Severe Atopic Dermatitis ◽

T Helper ◽

T Helper 1 ◽

Th2 Response ◽

Alopecia Universalis ◽

T Helper 2 ◽

Relapsing Remitting

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of nonscarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

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