Treatment of plaque-psoriasis in HIV-positive patients.

Psoriasis is a chronic inflammatory disease that can often accompany human immunodeficiency virus (HIV) epidemics. Development of psoriasis in HIV patients is correlated with a decrease in CD4+ count. Significant variability in the clinical presentation of psoriasis makes it a challenging disease to diagnose. Furthermore, associated immunodeficiency complicates standard treatment with immunosuppressive and biological therapy. Articles that match the terms psoriasis and HIV were searched in MEDLINE and Embase and selected based on their relevance. Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat HIV infection. In treating mild psoriasis in HIV-positive patients, topical agents combined with HAART are considered first-line therapy, followed by phototherapy. Second-line therapy includes oral retinoids, alone or combined. In treating challenging cases, apremilast has been used due to its lack of immunosuppressive effect. In case of progressive and refractory disease, limited data from studies suggest that immunosuppressive or biological therapy may be effective. Treatment of psoriasis in HIV patients remains a challenge, which is largely attributable to its complicated etiopathology and lack of an approved therapy option. In treating severe psoriasis, close collaboration with an infectious disease specialist is highly recommended. Further research is needed, preferably with an aim toward developing individualized therapy.

Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

Supplement Individual Article: A Reappraisal of Fixed-Combination Halobetasol Propionate and Tazarotene for the Treatment of Psoriasis: Biological Underpinnings, Therapeutic Mechanisms, and Economic Considerations.

Psoriasis is a complex inflammatory disease, which can be triggered by the interplay among keratinocytes, various immune cells, and even dermal vascular endothelial cells. Understanding of the key players and cytokine/chemokine messengers involved in the initiation and maintenance of psoriasis has significantly evolved and led to numerous systemic biologic therapies targeting those specific components. These therapies, despite their successes, do not ubiquitously affect all pathogenic cellular pathways. They also carry their risks and may be contraindicated in certain patient populations. Therefore, other therapeutics are still necessary. Tazarotene, a decades-old topical retinoid, has been successfully used for treating cutaneous psoriasis. Its retinoid effect via binding to retinoic acid receptors (RAR)/retinoic X receptors (RXR) alters cellular gene expression of numerous pathogenic cells and leads to a long-standing maintenance effect despite discontinuation - a phenomenon known as remittance. Concurrent use of tazarotene with topical corticosteroids results in reduced incidence of treatment-related adverse events. A fixed-combination lotion containing halobetasol propionate (HP) and tazarotene (HP 0.01%/TAZ 0.045%, Duobrii, Ortho Dermatologics) was developed implementing polymeric emulsion technology that demonstrates efficacy in psoriasis while mitigating adverse events associated with each component alone as monotherapy. In this paper, we review the pathogenesis of psoriasis and illuminate the effect of tazarotene and HP on key cellular pathways. In addition, we review the clinical efficacy of fixed-combination HP 0.01%/TAZ 0.045% lotion in psoriasis as well as its long-term treatment maintenance, applicability in skin of color, and beneficial economic impact for patients and healthcare stakeholders. As HP 0.01%/TAZ 0.045% lotion is safe and exhibits excellent efficacy, it should be within the therapeutic toolbox for every psoriasis patient.J Drugs Dermatol. 2023;22:1(Suppl 1):s3-10.

Treatment Options for Juvenile Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris represents a group of familial and acquired disorders of cornification that affect both adult and pediatric patients. Treatment options are difficult to assess through clinical trials, given the rarity of the disorder and its tendency for spontaneous remission. Case reports and case series are therefore the primary means of assessment. Because of the heterogeneity of the disease, there is no universal approach to treatment, and multiple agents may need to be trialed to achieve disease control. At present, topicals are used for most pediatric patients, though monotherapy with topicals is only effective for less severe disease. Despite concerns over their side-effect profiles, oral retinoids are generally accepted as a first-line systemic therapy. However, interleukin-17 inhibitors and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, may soon become first-line systemic treatment as well, given their efficacy and relative safety in trials thus far. Ustekinumab, in particular, is emerging as a first-line agent for patients with pityriasis rubra pilaris with CARD14 gene variations. When these therapies fail, second-line and adjunctive therapies to consider include tumor necrosis factor-alpha inhibitors, methotrexate, and phototherapy. However, further investigation is necessary to assess the safety and efficacy of many of these agents in juvenile pityriasis rubra pilaris.

Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

SUPPLEMENT INDIVIDUAL ARTICLES: Update on Truncal Acne: A Review of Treatments for a Neglected Disease and the Re-Emergence of Tazarotene.

Acne vulgaris of the trunk carries with it a major psychosocial impact and an unmet need for adequate management. Approximately 50% of patients with facial acne also exhibit involvement of the back, chest, and/or upper arms. The trunk poses a therapeutic challenge given its occlusion by clothing, the tendency for mechanical rubbing, a sebum physiology that differs from the face, as well as the fact that there is a large surface area for topical therapies to cover. Furthermore, truncal acne is underreported for a variety of reasons such as cultural barriers, sentiments of embarrassment, and prioritization of facial acne. To date, few medications have been studied specifically for truncal acne. In this article, an updated review of truncal acne and available therapies is provided. The most recent evidence for tazarotene, a third-generation retinoid previously approved for psoriasis and facial acne vulgaris over two decades ago, is also reviewed and compared to trifarotene, a fourth-generation retinoid that is the only approved tropical retinoid for both facial and truncal acne. J Drugs Dermatol. 2022;21:12(Suppl):s5-14.

Adapalene/benzoyl peroxide gel 0.3%/2.5% for acne vulgaris

Acne vulgaris is typically treated with a combination of a topical retinoid plus an antimicrobial agent, as recommended by national and international evidence-based guidelines around the globe. Adapalene, a synthetic topical retinoid, is available in two concentrations (0.1% and 0.3%) and in once-daily fixed-dose combinations with benzoyl peroxide (BPO) 2.5%. Adapalene 0.3%/BPO 2.5% is approved for use for moderate-to-severe acne with proven efficacy, good safety and tolerability across a spectrum of patient variables (different ages, genders, and skin types) and disease severity. While some patients experience issues with transient tolerability during retinoid and BPO therapy, it is our clinical experience that good patient education to set expectations and provide strategies to minimize irritation can overcome the majority of issues. This article reviews the data supporting the use of adapalene 0.3%/2.5% in practice, including the complementary mechanism of action of adapalene and BPO, clinical data from a range of settings, and key aspects of patient education.

SUPPLEMENT ARTICLE: Retinol: The Ideal Retinoid for Cosmetic Solutions.

Retinoids are a mainstay of dermatologic therapy. Although prescription retinoids are more potent than over the counter retinoids, when properly formulated cosmetic retinoids offer consumers an easily accessible, reasonably priced therapeutic option. Retinol has been shown to improve fine lines and wrinkles, hyperpigmentation, skin roughness, and the appearance of photoaged skin. The efficacy and tolerability of retinol makes it preferable to prescription retinoids as many patients are intolerant of these more potent forms. In this review, we will discuss the pharmacokinetics of retinol and the clinical studies confirming its efficacy, tolerability, and safety with long-term use. J Drugs Dermatol. 2022;21:7(Suppl):s4-10.

The Use of Bakuchiol in Dermatology: A Review of In Vitro and In Vivo Evidence.

The plant Psoralea corylfolia contains compounds such as psoralens that are useful for the treatment of psoriasis and vitiligo, and the plant is used in Chinese and Indian traditional medicine for diseases such as psoriasis and leprosy. Bakuchiol, a meroterpene phenol in Psoralea corylfolia, has similar functional properties to topical retinoids, which are commonly used to treat acne, post-inflammatory hyperpigmentation, and wrinkles. Bakuchiol’s anti-inflammatory and anti-proliferative properties also may lead to improvement in psoriasis and skin cancers, yet more clinical evidence is needed to elucidate these effects. Notably, bakuchiol does not cause common adverse effects seen with topical retinoids such as burning and scaling, permitting wider use in patients with sensitive skin. This review will detail the current evidence for bakuchiol as an alternative treatment in dermatologic conditions. J Drugs Dermatol. 2022;21(6):624-629. doi:10.36849/JDD.6740.

Efficacy of a retinoid complex plus anti-inflammatory component cream alone or in combination with prebiotic food supplement in adult acne: A randomized, assessor-blinded, parallel-group, multicenter trial on 184 women.

BACKGROUND: Adult female acne (AFA) nowadays is a very common skin condition affecting mainly women aged between 25 and 40. The treatment of AFA could be challenging. STUDY AIM: We evaluate and compare the efficacy and tolerability of a cream formulation containing two retinoid molecules (hydroxypinacolone/retinyl palmitate) combined with Iris Florentina root extract and a complex of three oligopeptides (C) applied twice a day (morning and evening) alone or in combination (C + O) with a food supplement containing a mixture of prebiotic molecules (FOS&GOS) zinc, lactoferrin, and niacinamide. SUBJECTS AND METHODS: In a multicenter, randomized, assessor-blinded, 12-week trial, we assessed the efficacy of these two regimens in the evolution of AFA lesions (non-inflammatory: NI-L; inflammatory: IL; and total number of lesions: TL). Additional efficacy endpoints were the evolution of the 6-point (from 0 to 5) GEA and Adult Female Acne Scoring Tool (AFAST) scores. RESULTS: One hundred and eighty-four women (mean age 32 ± 6 years) with AFA agreed to participate after obtaining informed consent. They were randomized (2:1) to the topical product (n = 123) (Group C) or to the combination (n = 61) (Group C + O) treatment. All enrolled patients concluded the trial with no drop-out. At baseline, NI-L, IL, and TL acne lesion count were 15 ± 9, 9 ± 5, and 24 ± 14 in the Group C and 19 ± 8, 9 ± 4, and 29 ± 10 in Group C + O. In comparison with the number of the acne lesions at the baseline, both treatment regimens induced a significant reduction (p = 0.0001, ANOVA test) at Week 12 in NI-L, IL, and TL by -54%, -63%, and - 59% in Group C and by -55%, -73%, and - 61% in the Group C + O, respectively. At Week 12, the absolute IL count reduction vs. baseline was significantly (p = 0.0158) greater in Group C + O (-7.0) in comparison with Group C (-5.5). The GEA absolute score reduction in Group C + O group was significantly greater in comparison with Group C (-1.5 vs. -1.1; p = 0.0097). In the Group C + O, a greater percentage of success treatment (defined as a GEA score of 0/1 at Week 12) was observed in comparison with Group C (39% vs. 27%; p = 0.06). AFAST score at baseline was 2.4 ± 0.5 in group C and 2.8 ± 0.6 in group C + O. AFAST score was reduced by 21% and by 51% after 6 and 12 weeks of treatment in group C and by 22% and 55% in group C + O, respectively. Both treatment regimens were well tolerated. Not relevant adverse events were recorded. CONCLUSION: A cream containing retinoid molecules and Iris Florentina root extract is effective and well tolerated in the management of AFA. The treatment combination with a prebiotic and anti-inflammatory food supplement offers an additional clinical benefit mainly in reducing inflammatory lesions and improving the severity acne score.

Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review.

Genodermatoses are genetically inherited dermatologic conditions. The management of cutaneous findings in genodermatoses is challenging, and first-line therapies, such as steroids and/or retinoids, are often inadequate. In recent years, research on the molecular basis of genodermatoses has led to the use of biologic therapies for intractable disease. Here, we review the evidence regarding the use of available biologic therapies for the management of dermatologic findings in genodermatoses. Biologic therapies appear to be promising therapeutic options for several recalcitrant genodermatoses, especially those with underlying immune dysregulation. However, not all genodermatoses are amenable to biologic therapies, and some have been shown to paradoxically worsen under treatment. Biologic therapies offer a novel avenue to target refractory genodermatoses. However, evidence supporting the use of biologic therapies in the management of genodermatoses is mostly limited to case reports and case series. Further studies are warranted to determine the safety and efficacy of biologic therapies for the management of cutaneous findings in genodermatoses.

Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway.

BACKGROUND: Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance. METHODS: Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs). RESULTS: Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an IC50 superior to that of acyclic retinoid and sorafenib, to which the recurrent HCC exhibits significant resistance at advanced stage. Sulfarotene promoted the expression and activation of RARα, which down-regulated SOS2, a key signal mediator associated with RAS activation and signal transduction involved in multiple downstream pathways. Moreover, sulfarotene selectively inhibited tumorigenesis of HCC PDXs with high expression for SOS2. CONCLUSIONS: Our study identified sulfarotene as a selective inhibitor for the TRCs of HCC, which targets a novel RARα-SOS2-RAS signal nexus, shedding light on a new, promising strategy of target therapy for advanced liver cancer.

How we treat advanced stage cutaneous T-cell lymphoma - mycosis fungoides and Sézary syndrome.

T-cell lymphomas (TCLs) constitute a rare subset of non-Hodgkin lymphomas, with mycosis fungoides/Sézary syndrome (MF/SS) being the most common subtype of cutaneous TCLs (CTCLs). Considered an incurable but treatable disease, MF/SS management presents several challenges including diagnostic delays, debilitating effect on patients' quality of life, need for several lines of therapies, multidisciplinary care and cumulative drug toxicities limiting duration of use. The present review intends to provide an overview of the recent advances in our understanding of the biology of CTCL and how these are being leveraged to provide additional treatment options for management of advanced and recurrent disease. In addition, the discussion of the different modalities of treatment is summarised to further outline the importance of multidisciplinary care and early referral to CTCL centres.

Retinoids in Cutaneous Squamous Cell Carcinoma.

Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However, humans usually die from vitamin A deficiency before cancers have time to develop. A recent long-term cohort study found that high dietary vitamin A reduced the risk of cutaneous squamous cell carcinoma (cSCC). cSCC is a form of nonmelanoma skin cancer that primarily occurs from excess exposure to ultraviolet light B (UVB). These cancers are expensive to treat and can lead to metastasis and death. Oral synthetic retinoids prevent the reoccurrence of cSCC, but side effects limit their use in chemoprevention. Several proteins involved in vitamin A metabolism and signaling are altered in cSCC, which may lead to retinoid resistance. The expression of vitamin A metabolism proteins may also have prognostic value. This article reviews what is known about natural and synthetic retinoids and their metabolism in cSCC.

Retinoid combined with photodynamic therapy against hyperkeratotic chromoblastomycosis: A case report and literature review.

Chromoblastomycosis (CBM) is a chronic granulomatous fungal infection caused by melanised or brown-pigmented fungi. It can lead to chronic persistent infections and may cause incapacity for labour in some severe clinical forms. The optimal therapy for CBM is still uncertain. Here, we reported the case of a 66-year-old male who has had red plaque and recurrent keratinised protrusions on his right forearm for 20 years. He was treated orally with terbinafine, itraconazole and isotretinoin. He also received carbon dioxide(CO2 ) laser to eradicate the keratinised protrusions and promote the penetration of photosensitiser. After the CO2 laser, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) was adopted immediately to inhibiting the growth of fungi in subcutaneous tissue. The patient received an important improvement with a plaque and crust reduction after 4 months. For such recalcitrant case of chromoblastomycosis, the use of retinoid, CO2 laser combined with ALA-PDT may be a new adjuvant therapy. We further reviewed the cases of chromoblastomycosis treated with laser, photodynamic therapy or retinoic acid.

Acne fulminans.

Acne fulminans (AF) is a rare and severe form of inflammatory acne presenting clinically with an abrupt outburst of painful, hemorrhagic pustules and ulceration, that may or may not be associated with systemic symptoms, such as fever, polyarthritis, and laboratory abnormalities. It typically affects male teenagers with a pre-existing acne. Although the pathogenetic mechanism has not been established yet, a role of genetic, abnormal immunologic response, drugs intake, hormonal imbalance and viral infection, as causal factors, has been identified. AF may occur as a single disease or may be associated with other disorders. Traditionally, AF has been classified, on the basis of the presence of systemic involvement, in "acne fulminans" and acne fulminans "sine fulminans," when no systemic involvement is present. Recently, four clinical variants have been proposed: acne fulminans with systemic symptoms (AF-SS), acne fulminans without systemic symptoms (AF-WOSS), isotretinoin-induced acne fulminans with systemic symptoms (IIAF-SS), isotretinoin-induced acne fulminans without systemic symptoms (IIAF-WOSS). The diagnosis of AF is usually based on clinical history and physical examination. No specific laboratory abnormalities are generally found. In selected cases, biopsy and/or radiologic imaging are helpful for a correct diagnosis. The treatment significantly differs from severe acne according to severity of clinical presentation and possible systemic involvement. Currently, systemic corticosteroids (prednisolone) and retinoids (isotretinoin) represent the first choice of treatment. Dapsone, cyclosporine A, methotrexate, azathioprine, levamisole, and biological agents such as anakinra, infliximab, adalimumab may be considered as alternative therapies in selected cases. Adjunctive topical and physical therapies may also be considered.

Real-world use of extracorporeal photopheresis for patients with cutaneous T-cell lymphoma in the United States: 2010-2015.

Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL).Objective: To investigate real-world use of ECP in CTCL patients in the US.Methods: Data from the Truven MarketScan® database (2010-2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients.Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p < .05), rates of organ transplant (49.6% vs 7.8%, p < .001), and graft vs host disease (41.9% vs 3.4%, p < .001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p = .001).Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay.

Recognition, diagnosis, and treatment of hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic skin condition characterized by recurrent painful abscesses usually limited to the intertriginous areas. Global prevalence has been estimated at up to 4% of the population. The exact pathogenesis of hidradenitis suppurativa is yet to be elucidated; however, recent research has shown that the disease occurs under the influence of multiple genetic, environmental, and lifestyle factors. Repeated insults result in sinus tract formation and disfigurement, which can have a significant psychosocial effect on patients. A wide range of treatments are available but none are curative. A combination antibiotic regimen is considered first line, and research into the use of biologics has been promising. Early recognition and treatment is paramount to achieving a better prognosis and improving patient quality of life.

Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies.

Background: Breast cancer patients have a lifelong 2-4-fold increased risk of developing a second primary tumor in the contralateral breast compared with the risk for a first primary breast cancer in the general female population. Prevention of contralateral breast cancer (CBC) has received increased attention during recent decades. Here, we summarize and discuss the available literature on drug preventive therapy and CBC.Results: The endocrine-targetting drugs, tamoxifen and aromatase inhibitors are used as standard adjuvant treatment for estrogen receptor (ER)-positive breast cancer. Both are associated with relative risk reductions of CBC of up to 50%, but incur serious side effects. Several prescription drugs originally developed for other purposes, including bisphosphonates, statins, non-steroidal anti-inflammatory drugs, metformin, anti-hypertensives and retinoids, have shown anti-cancer activity in preclinical models. However, results of observational studies on CBC are sparse and inconsistent, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients.Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies.

An Accord of Nuclear Receptor Expression in CD4+ T Cells in Rheumatoid Arthritis.

Chronically activated CD4+ T cells drive uncontrolled inflammation, leading to tissue damage in various autoimmune disorders, such as rheumatoid arthritis (RA). Investigation of the molecular mechanisms involved in RA and recent analysis of transcriptomic profiles has implicated members of the nuclear receptor (NR) superfamily in RA. NRs are required for the development, differentiation, and effector function of CD4+ T cells; therefore, it is thought that NRs are important in shaping the CD4+ T cell repertoire and associated inflammation in RA. Despite their relevance, the full potential of the NR superfamily in RA, either as biomarkers or disease targets, has not been harnessed. To gain insight on the NR members that are closely associated with RA disease activity, we generated an expression atlas for the NR superfamily in CD4+ T cells isolated either in a steady state or over the course of collagen-induced arthritis mouse model of RA. We observed discrete expression patterns among the NR superfamily during the disease stages. NRs that instigate anti-inflammatory programs underwent major downregulation during disease onset; however, during the fully developed disease stage we noticed that NRs that induce proinflammatory programs had reduced transcript levels. These animal findings corroborated well with the expression patterns of NRs in clinical samples obtained from RA patients. Furthermore, we observed that targeting NRs using synthetic ligands alleviates the progression of collagen-induced arthritis. Overall, our data demonstrates the potential of the NR superfamily as novel therapeutic targets for the treatment of autoimmune disorders.