Study on inhibitory effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating the upstream and downstream cytokines of type Ⅱ innate lymphoid cells / 中国药房

OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Progress of the relationship between group 2 innate lymphoid cells and bronchial asthma / 国际儿科学杂志

Group 2 innate lymphoid cells (ILC2) are a newly identified subset of innate immune cells which are closely associated with the development of bronchial asthma(asthma). ILC2 develops from lymphoid progenitor cells in the bone marrow under the regulation of retinoid-related nuclear orphan receptor α (RORα) and GA-TA-binding protein-3 (GATA-3). ILC2 can be activated by IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and lipid mediator and produce Th2 cytokines, such as IL-4, IL-5, IL-9 and IL-13, which activate innate immune cells and adaptive immune cells to participate in asthma inflammation.ILC2 may be a therapeutic target for asthma, providing new possibilities for the prevention and treatment.

Nuocytes from mesenteric lymph node promote allergic responses in a mouse model / Nuócitos de linfonodo mesentérico promovem respostas alérgicas em um modelo de camundongo

Abstract Introduction: Nuocytes play an important role in Type 2 immunity. However, the contribution of ILC2s to allergic rhinitis remains to be clearly elucidated. Objective: To evaluate the role of nuocytes from mesenteric lymph node on allergic responses in mice. Methods: After intraperitoneal administration of interleukin IL-25 and IL-33 to wild-type and Il17br-/-Il1rl1-/- double-deficient mice, nuocytes were purified from the the nasal-associated lymphoid tissue and mesenteric lymph nodes. Then, we assessed productions of IL-5 and IL-13 in nuocytes' cultures. Finally, we adoptively transferred the mesenteric lymph node-derived nuocytes from wild-type and Il17br-/-Il1rl1-/- mice to the murine model of allergic rhinitis to evaluate their roles in nasal allergic responses. Results: We showed that nuocytes in the mesenteric lymph nodes of wild-type mice were upregulated after application of IL-25 and IL-33, and were induced to produce IL-5 and IL-13. Numbers of sneezing and nasal rubbing as well as eosinophils were all enhanced after the adoptive transfer of wild-type nuocytes. Concentrations of IL-5, IL-13, IL-25 and IL-33 in nasal lavage fluid of allergic mice were also increased. However, nuocytes fromIl17br-/-Il1rl1-/- mice did not increase sneezing and nasal rubbing and eosinophilia, and upregulate the above cytokines in the nasal lavage fluid. Conclusion: The findings demonstrate that nuocytes from the mesenteric lymph nodes of wildtype mice promote allergic responses in a mouse model.

Resumo Introdução: Os nuócitos desempenham um papel importante na imunidade do tipo 2. No entanto, a contribuição das interleucinas ILC2s na rinite alérgica ainda precisa ser elucidada. Objetivo: Avaliar o papel dos nuócitos de linfonodos mesentéricos nas respostas alérgicas em camundongos. Método: Após a administração intraperitoneal de interleucina (IL)-25 e IL-33 em camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- com deficiência dupla, os nuócitos foram purificados do tecido linfoide associado a mucosa nasal e linfonodos mesentéricos. Em seguida, avaliamos as produções de IL-5 e IL-13 em culturas de nuócitos. Finalmente, transferimos adotivamente os nuócitos derivados de linfonodos mesentéricos de camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- para o modelo murino de rinite alérgica para avaliar seu papel nas respostas alérgicas nasais. Resultados: Mostramos que os nuócitos nos linfonodos mesentéricos de camundongos do tipo selvagem estavam up-regulados após a aplicação de IL-25 e IL-33 e foram induzidos a produzir IL-5 e IL-13. Os espirros e friçcão nasal, bem como os eosinófilos, aumentaram após a transferência adotiva de nuócitos do tipo selvagem. As concentrações de IL-5, IL-13, IL-25 e IL-33 no líquido da lavagem nasal de camundongos alérgicos também estavam aumentadas. Entretanto, os nuócitos de camundongos Il17br-/-Il1rl1-/- não aumentaram os espirros e a friçcão nasal ou eosinofilia e up-regularam as citocinas acima no líquido de lavagem nasal. Conclusão: Os achados demonstram que os nuócitos dos linfonodos mesentéricos de camundongos selvagens promovem respostas alérgicas em um modelo de camundongo.

Control of Innate and Adaptive Lymphocytes by the RAR-Retinoic Acid Axis

Lymphocytes, such as T cells, B cells, and innate lymphoid cells (ILCs), play central roles in regulating immune responses. Retinoic acids (RAs) are vitamin A metabolites, produced and metabolized by certain tissue cells and myeloid cells in a tissue-specific manner. It has been established that RAs induce gut-homing receptors on T cells, B cells, and ILCs. A mounting body of evidence indicates that RAs exert far-reaching effects on functional differentiation and fate of these lymphocytes. For example, RAs promote effector T cell maintenance, generation of induced gut-homing regulatory and effector T cell subsets, antibody production by B cells, and functional maturation of ILCs. Key functions of RAs in regulating major groups of innate and adaptive lymphocytes are highlighted in this article.

Research progression of interleukin 22 and inflammatory bowel disease / 医学研究生学报

Inflammatory bowel disease (IBD) is a type of multi-etiology-induced, abnormal immune-mediated chronic recurrent inflammation of the intestine, which includes ulcerative colitis (UC) and Crohn's disease,(CD). IL-22 is a cytokine with unique biological properties. In the intestine, IL-22 has the ability to promote the expression of antimicrobial peptides and mucins that promote mucosal barrier integrity by activating the STAT3 pathway, and may promote intestinal epithelial cell regeneration and enhance intestinal epithelial cell barrier function. IL-22 is significantly increased in the intestinal mucosa of IBD patients. IL-22 can promote the repair of intestinal inflammatory damage, but with environmental changes, such as the level of expression of IL-23, T-bet, IL-22 binding protein, IL-22displayed dural characteristic, on the one hand, it can promote the repair of inflammatory injury, on the other hand it will increase the inflammatory injury response. This article mainly explains the origin of IL-22, its mode of action, and its application prospects in clinical treatment.

ILC2 regulates chronic renal failure patients' immunity by secretion of IL-13 through activating of STAT6 / 中国病理生理杂志

AIM: To explore the effect and possible mechanism of type 2 innate lymphoid cell (ILC2) on the development of chronic renal failure (CRF).METHODS: The patients with chronic renal failure (n=36) in the Fist Affiliated Hospital of Sun Yat-sen University from March 2016 to December 2016 were selected, and 32 healthy persons in the same period were enrolled in the study for control.The proportion of ILC2 in the PBMC of CRF patients and healthy controls was detected by flow cytometry, IL-13 concentration in the plasma was measured by ELISA.The isolated PBMCs from the patients and healthy persons were divided into 3 groups (control group, cytokine group, intervention group) and cultured in vitro for 3 days, respespestively, then IL-13 concentration was measured by ELISA.The protein levels of phosphorylated signal transducers and activators of transcription 6 (p-STAT6) in the PBMC of healthy controls before stimulation and after stimulation for 15 min, 30 min, 1 h, 2 h were determined by Western blot.RESULTS: The proportion of ILC2 in the PBMC and the plasma IL-13 concentration of CRF patients was higher than that in the healthy controls (P<0.05).In the culture supernatant in vitro, IL-13 concentration in the 3 subgroups of CRF patients (control group, cytokine group, intervention group) were all higher than that in the healthy controls (P<0.05), both the 2 groups showed a trend that the active IL-13 concentration in cytokine group was higher than that in control group, and that in intervention group was lower than that in cytokine group.The protein levels of p-STAT6 in cytokine stimulated-PBMC with a time dependent manner.CONCLUSION: The percentage of ILC2 in the PBMC is elevated in CRF patients.Furthermore, the ILC2 secret large amount of IL-13 to mediate the polarization of Th2 cells to regulate immunity through activating p-STAT6.

Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases / 中华耳鼻咽喉头颈外科杂志

Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

Establishment and function of tissue-resident innate lymphoid cells in the skin

Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

Role of type II innate lymphoid cells in browning of white adipose tissue / 中国病理生理杂志

Type II innate lymphoid cells ( ILC2s) are widely distributed in the blood , intestines, trachea, lung, spleen, liver, animal fat and skin, and involved in the innate immune responses .ILC2s have attracted much atten-tion for its important roles in the conversion of white adipose to beige adipose .Studies have shown that ILC2s are essential for the proliferation and differentiation of adipocyte precursor cells , and they also play a vital role in anti-parasitic infection and allergic inflammation .This review discusses the discovery , differentiation , development , distribution and function of ILC2s, and their relationships with the browning of white adipose tissue for providing valuable references on understanding the pathogenesis , prevention and treatment of obesity and fat metabolism disorders .

Unusual Suspects in the Development of Obesity-Induced Inflammation and Insulin Resistance: NK cells, iNKT cells, and ILCs

The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity.

Functional Defects in Type 3 Innate Lymphoid Cells and Classical Monocytes in a Patient with Hyper-IgE Syndrome

Hyper-IgE syndrome (HIES) is a very rare primary immune deficiency characterized by elevated serum IgE levels, recurrent bacterial infections, chronic dermatitis, and connective tissue abnormalities. Autosomal dominant (AD) HIES involves a mutation in signal transducer and activator of transcription 3 (STAT3) that leads to an impaired T(H)17 response. STAT3 signaling is also involved in the function of RORγt⁺ type 3 innate lymphoid cells (ILC3s) and RORγt⁺T(H)17 cells. The aim of this study was to investigate the role of innate immune cells such as innate lymphoid cells (ILCs), granulocytes, and monocytes in a patient with HIES. Peripheral blood mononuclear cells (PBMCs) from a patient with HIES and three age-matched healthy controls were obtained for the analysis of the innate and adaptive immune cells. The frequencies of ILCs in PBMCs were lower in the patient with HIES than in the controls. Moreover, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A produced by ILC3s in PBMCs were lower in the patient with HIES than the controls. Compared with the controls, classical monocytes (CD14⁺CD16(low)), which have a high antimicrobial capability, were also lower in the patient with HIES, while non-classical monocytes (CD14(low)CD16⁺) as well as intermediate monocytes (CD14⁺CD16(intermediate)) were higher. Taken together, these results indicate that the impaired immune defense against pathogenic microbes in the patient with HIES might be partially explained by functional defects in ILC3s and inflammatory monocytes.

Innate Lymphoid Cells and Infection

The functions of innate lymphoid cells (ILCs) have been known to play an important role in immunity and immune responses. ILCs are rapidly-responding cells that are involved in tissue remodeling, cancer, the regulation of autoimmune inflammation and resistance to pathogens. Understanding the role of ILCs in regulating immune response could be useful for the development of new therapeutic strategies against emerging or re-emerging infectious diseases. However, the relevance of ILCs in infectious diseases was not fully uncovered. This review provides an overview of the current knowledge of the functional characteristics of ILCs and how these cells interact with pathogens to mediate immune responses.

Latest progress and prospect of anti-inflammatory immunopharmacology in China / 中国药理学与毒理学杂志

Since the first session of Chinese anti-inflammatory immunopharmacological society in 1982,many breakthroughs of immunological research have been made in western countries,such as identification of pathogens by natural immune cells,regulation of immune response,lymphocyte differ?entiation and development. At the same time,much progress has been achieved in anti-inflammatory and immunological research in China,especially in the field of basic scientific issues in immunology, frontier and hot topics,immunological mechanisms of major diseases and related drugs. The course of development of Chinese anti- inflammatory immunopharmacological research has experiences various stages,such as ″follow ″ in the past to ″work together ″ and to ″lead ″ in some research areas in today′s international immunology.

Roles of type 2 innate lymphoid cells in the pathogenesis of bronchial asthma / 中华微生物学和免疫学杂志

Type 2 innate lymphoid cells ( ILC2s) are recently identified members of the innate lymphoid cell ( ILC) family. These cells are capable of producing Th2-type cytokines such as IL-5 and IL-13 in response to epithelial cell-derived cytokines IL-25 and IL-33 and play critical roles in allergic diseases such as bronchial asthma. Further investigations on ILC2s will enhance the better understanding of type 2 immune responses and may provide new strategies for the treatment of allergic asthma. In this review, we fo-cus on the origin, location and biological function of ILC2s as well as their possible roles in the pathogenesis of bronchial asthma.

On optimum conditons for establishment of calcipotriol-induced mouse atopic dermatitis model / 中国药理学通报

Aim To investigate the method of establishing the atopic dermatitis mice model induced by calcipotriol ( MC903 ) . Methods Induction dose exploratory experiment: since d 0, 0.33,1,3 nmol MC903 was smeared on the right ear of BALB/c mice in each dose group respectively , for 7 consecutive days . The ear swelling degree of the mice was observed every day and the bilateral ears thicknesses were measured .The materials were drawn and analyzed in d 3 and d 7.Induction days exploratory experiment: 2 nmol MC903 was smeared on the right ear of BALB/c mice, for 14 consecutive days .The ear swelling degree of mice was observed every day and the bilateral ears thicknesses were measured .The histopathological examination of the right ear was conducted in 3 d, 7 d, 11 d and 15 d respectively .The tissue homogenate of the mice right ear was prepared .The ex-pressions of thymic stromal lymphopoietin (TSLP),IL-33, IL-4 and IFN-γin the homogenate , CD40 +,CD86 +,the DC surface markers and ILC2 contents in the peripheral lymph nodes were detected.Results ①1,3 nmol MC903 induced ear swelling in mice was significantly increased in d 3, the levels of TSLP and IL-4 were significantly increased .The level of IL-33 in 3 nmol dose group was increased significantly in d 7.② The right ear swelling of 2 nmol MC903 induced atopic dermatitis mice was significant , the ear thickness was increased gradually and reached the peak in d 14.The histopathological examination of the mice ear tissue showed in d 7, the right ear tissue of the mice was swelling and red , the capillary vessels were dilated and the infiltration of inflammatory cells was obvious .The ear in-flammatory symptoms maintained and gradually aggravated for 15 days.Compared with the normal mice , MC903 increased the TSLP level in the right ear tissue homogenate significantly in d 3 and then decreased gradually .The levels of IL-4 and IL-33 were increased significantly in d 7 and then decreased gradually .The levels of ILC2, CD40 +, CD86 + in the peripheral lymph nodes were increased in d 7 and d 15.Conclusion The atopic derma-titis mice model can be successfully established using 2 nmol MC903 induced mice for 7 days.Appropriate testing point of TSLP is d 3.Appropriate testing point of IL-33 and IL-4 is d 7.

Functions of innate lymphoid cells in inflammatory bowel disease / 医学研究生学报

Innate lymphoid cell is a type of newly discovered innate immune cell , which can function as adaptive T cells . Based on the transcription factors and the expression of effector cytokines , innate lymphoid cells can be categorized into three sub-groups:ILC1, ILC2 and ILC3.The inflammatory factors these produced by ILC play an important role in the development of inflamma -tory bowel disease (IBD), but ILC3 can secrete IL-22, which promotes the restoration of intestinal epithelial cells .Exploring the func-tion of ILC has a great significance in the treatments of IBD .This article reviews their phenotype , function and also relationship with IBD.

Advances in innate lymphoid cells / 中国免疫学杂志

Natural killer (NK) cells have long been considered the only representative of lymphocyte lineages among the innate immune system ,but recent studies have revealed that several types of innate lymphoid cells ( ILC ) exist in both humans and mice.These newly identified ILC populations were mainly distributed at mucosal barriers ,regardless of their rarity ,they play important roles in the defense against pathogens and in the maintenance of tissue or organ homeostasis .In the early stages of ILC development ,a common ILC lineage-restricted progenitor exists and under the control of different transcription factors ,the progenitor can later give rise to different ILC subsets with distinct phenotypes and functions.Different ILC subsets exhibit distinct cytokine secretion profiles ,based on the categorization of helper T cell subsets , ILC family has been further classified into three groups.The finding of diverse ILC extremely enriches the content of innate immunity ,and also provides new insights into links between innate and adaptive immunity .

Pay more attentions to the complexity of the resident immune cells in ocular surface / 中华实验眼科杂志

Ocular surface is a special interface between the inner ocular tissue and the external environment.It provides effective physical and biological barriers to prevent environmentally harmful substances and pathogenic microbes invading into the eye.This protection is afforded by unique local anatomy and cellular components, especially the resident immune cells such as innate lymphoid cells (ILCs), macrophages, mast cells, Langerhans cells(LCs) and γδ T cells.Recent studies reinforce the importance of LCs and mast cells as inducers of immune tolerance.Most adult tissue macrophage populations are seeded before birth and maintained in the steady state independently of monocytes from blood.However, under inflammatory condition, some transient monocytes enter into tissue and become macrophage compartments.Monocytes are subdivided into two main phenotypically and functionally distinct subsets.The first main subset is dedicated to the surveillance of endothelial integrity.The second main subset compasses classical monocyte functions such as rapid migration to the sites of injury and the replenishment of peripheral dendritic cells and macrophage compartments.In addition, newly identified ILCs are founded in the ocular surface tissues.These cell groups defens the different stimulus from external environment by producing different cytokines and growth factors.Accumulating data highlight some key roles of tissue-resident immune cells in ocular surface homeostasis and pathology.