Pineal-Thymus Interrelation in Maintenance of T-Cell Dependent Immune Responses in a Tropical Seasonal Breeder Funambulus pennanti
Keywords:F. pennanti, Immunity, Lymphoid Tissues, Pinealectomy, Thymectomy
AbstractCrosstalk between the neuro-endocrine axis and immune cells is documented in many laboratory and clinical studies. The pineal gland and its hormone melatonin play a central role in this network by positively regulating immune cell proliferation and differentiation via influencing the synthesis of immunomodulatory molecules. However, the pineal-thymus interaction in modulating their bi-directional communication remains elusive. In the present study we investigated the effect of pineal-thymus interaction on the structure and functional status of lymphoid tissues (i.e., spleen and lymph nodes) in a tropical seasonal breeder, F. pennanti. We observed that pinealectomy severely compromised the immune status of the squirrels. Besides pinealectomy, simultaneous ablation of pineal and thymus gland, further resulted in atrophy of the lymphoid tissues along with reduced total leucocyte and lymphocyte count. Exogenous melatonin administration improved the total leucocyte and lymphocyte count and restored T cell dependent immune responses and lymphoid tissue architecture in pinealectomized (Px) group. Our observations suggest that suppression of endogenous melatonin in Px group decreased the efficiency of the immune system probably by modulating the production of thymic factors, which becomes even severe with simultaneous ablation of the thymus and pineal gland, resulting in declined immune responsiveness. Thus, it can be inferred that the pineal melatonin and its interaction with thymus plays an important role in regulation of immune status of the squirrels.
Ahmad R, Haldar C. Photoperiod-testicular-immune interaction in a seasonal breeder Indian palm squirrel Funambulus pennanti during the reproductively inactive and active phases. J Neuroendocrinol. 2009; 21:2–9
Ben-Nathan D, Maestroni GJM, Lustig S, Conti A. Protective effect of melatonin in mice infected with encephalitis viruses. Arch Virol. 1995; 140:223–30.
Calvo JR, Rafii-El-Idrissi M, Pozo D, Guerrero JM Immunomodulatory role of melatonin: Specific binding sites in human and rodent lymphoid cells. J Pineal Res. 1995; 18:119–26.
Caroleo MC, Frasca D, Doria G. Melatonin as immunomodulatory in immunodeficient mice Immunopharmacology.1992; 23:81–9.
Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine. 2005a;.27:189–200.
Carrillo-Vico A, Lardone PJ, Alvarez-Sánchez N, RodríguezRodríguez A, Guerrero JM. Melatonin: buffering the immune system. Int J Mol Sci. 2013; 14:8638–83.
Carrillo-Vico A, Lardone PJ, Naji L, Fernández-Santos JM, Martín-Lacave I, Guerrero JM, Calvo JR. Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in mice: regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res. 2005b; 39:400–8.
Csaba G, Barath P. Morphological changes of thymus and the thyroid gland after postnatal extirpation of pineal body.Endocrinol Exp. 1975; 9:59–67.
Demas GE, Drazen DL, Jasnow AM, Bartness TJ, Nelson RJ. Sympathoadrenal system differentially affects photoperiodic changes in humoral immunity of Siberian hamsters (Phodopus sungorus). J Neuroendocrinol. 2002; 14:29–35.
Goldstein AL, Guha A, Zatz MM, Hardy A, White A. Proc Natl Acad Sci USA. 1972; 69:1800–3.
Goldstein G. Isolation of bovine thymic: A polypeptide hormone of the thymus. Nature. 1974; 247:11–4.
Greenstein BP, Fitzpatrick FTA, Adock IM, Kendall MD, Wheller MJ. Reapearance of the thymus in old rats after orchidetomy: Inhibition of regeneration by testosterone. J endocrinol. 1986; 110:417–22.
Greenstein BD, Adcock IMF, Kendal MD, Wheeler MJ. Reappearance of the thymus in old rats after orchidectomy; inhibition of regeneration by testosterone. J Endocrinol.1986; 110:417–22.
Guerin, BM, Fernandez E, Behhacene N, Toribio ML, Auberger P. CD 10 is expressed on human thymic epithetial cell lines and modulates thymopoietin induced cell proliferation.Faseb Journal. 1997; 11(12):1003–11.
Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocrinol Res. 1992; 18:91–113.
Guerrero JM, Reiter RJ. A brief survey of pineal gland–immune system interrelationships. Endocr Res. 1992; 18:91– 113.
Gupta S, Haldar C. Physiological crosstalk between melatonin and glucocorticoid receptor modulates T-cell mediated immune responses in a wild tropical rodent. Funambulus pennant. J Steroid Biochem Mol Biol. 2013; 134:23–36.
Gupta S, Haldar C. Photoperiodic modulation of local melatonin synthesis and its role in regulation of thymic homeostasis in Funambulus pennanti. Gen Comp Endocrinol.2015; 15:30044–7.
Haldar C, Hausler D, Gupta D. Effect of the pineal gland on circadian rhythmicity of colony forming units for granulocytes and macrophages (CFU-GM) from rat bone marrow cell cultures. J Pineal Res. 1992; 12:79–83.
Haldar, Mishra C. Method of pinealectomy in some vertebrates.Ind J Exp Biol. 1986; 24:319–22.
Haldar C, Saxena N. Antigonadotropic activity of pineal gland of the Indian palm squirrel Funambulus pennant. Indian J Exp Biol. 1989; 27:421–3.
Haldar C, Singh R. Pineal modulation of thymus and immune function in a seasonally breeding tropical rodent, Funambulus pennant. J Exp Zool. 2001; 289:90–8.
Haldar C, Singh R, Guchhait P. Relationship between the annual rhythms in melatonin and immune system status in the tropical palm squirrel, Funambulus pennant. Chronobiol Int. 2001; 18:61–9.
Haldar C, Rai S, Singh R. Melatonin blocks dexamethasoneinduced immunosuppression in a seasonally breeding rodent Indian palm squirrel, Funambulus pennant. Steroids.2004; 69:367–77.
Icten N, Kargoz F, Gunec KA. The effects of constant darkness and constant light on the pineal gland and thymus morphology in rats. Tr J Medical Sciences. 1998; 28:7–12.
Jankovic BD, Isakovic K, Horvat J. Effect of a lipid fraction from rat thymus on delayed hypersensitivity reactions of neonatally thymectomized rats. Nature. 1970; 208:256–7.
Kay M. The thymus: Clock for immunologic aging? J Invest Dermatol. 1979. 73:29–38.
Kuci S, Becker J, Veit G, Handgretinger R, Attanasio A, Bruchelt G, Treuner J, Niethammer D, Gupta D. Circadian variation in the immunomodulatory role of the pineal gland. Neuroendocrinol Let. 1988; 10:65–79.
Lissoni P, Barni S, Ardizzoia A, Paolorassi F, Crispino S, Tancini G, Tisi E, Architis C, De Toma D, Pipino G, Conti A, Maestroni GJM. Randomized study with pineal hormones versus supportive care alone in advanced non- small cell lung cancer resistant to first – line chemotherapy containing cisplastin . Oncology. 1992; 49:336.
Lochmiller RL, Ditchkoff SS. Environmental influences on mass dynamics of the cotton rat (Sigmodon hispidus) thymus gland. Biol Rhy Res. 1999; 29:206–12.
Maestroni GJM, Conti A, Lissoni A. Hematopoietic rescue via T-cell dependent endogenous GM–CSF by the pineal neurohormone melatonin in tumor bearing mice. Cancer Res. 1994; 54:2429–32.
Maestroni GJM, Conti A, Lissoni P. Colony stimulating activity and hematopoietic rescue from cancer chemotherapy compounds are induced by melatonin via endogenous interleukin4. Cancer Res. 1994; 54:4740–3.
Maestroni GJM, Conti A, Pierpaoli W. The pineal gland and the circadian opiatergic immunoregulatory role of melatonin.Ann N Y Acad Sci. 1987; 521:140–8.
Maestroni GJM, Conti A, Pierpaoli W. Role of pineal gland in immunity. II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin Exp Immunol. 1987; 68:384–91.
Maestroni GJM, Flamigni LF, Hertens H, Conti A. Biochemical and functional characterization of melatonin- inducedopioids in spleen and bone marrow T- helper cells.Neuroendocrinol Lett. 1995; 17:145–52.
Maestroni GJM. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res. 1995; 18:84–9.
Maestroni GJM. The immunoneuroendocrine role of melatonin.J Pineal Res. 1993; 14:1–10.
Maestroni GJM, Flamigni LF, Hertens H, Conti A. Biochemical and functional characterization of melatonin–induced– opioids in spleen and been marrow T-helper cells.Neuroendocrinol Lett. 1995; 17:145–52.
Makindoan T, Key MMB. Age influence on the immune system. Ads Immunol. 1980; 29:287–330.
Martin LB, Weil ZM, Nelson RJ. Seasonal changes in vertebrate immune activity: Mediation by physiological tradeoffs.Philos Trans R Soc Lond B Biol Sci. 2008; 363:321–39.
Kumar N, Shan L-X, Hardy MP, Bardin CW, Sundaram K.Mechanism of Androgen –Induced thymolysis in rats. Endocrinology.1995; 36(11):4887–93.
Osoba D, Millar JFAP. The lymphoid tissues and immune responsiveness of neonatally thymectomized mice bearing thymus tissues in millipore diffusion chambers. J Exp Med.1964; 119:177–94.
Pioli C, Carleo C, Nistico G, Doria G. Melatonin increases antigen presentation and amplifies specific and non-specific signals for T-cell proliferation. Int G Immunopharmacol.1993; 15:463–8.
Poon AM, Pang SF. 2[125I] iodomelatonin binding sites in spleens of guinea pigs. Life Sci. 1992; 50:1719–26.
Rafii-el-Idrissi M, Calvo JR, Pozo D, Harmouch A, Guerrero JM. Specific binding of [125I] iodomelatonin by rat splenocytes: Characterization and its role on regulation of cyclic AMP production. J Neuroimmunol. 1995; 57:171–8.
Rella W, Lapin V. Immunocompetence of pinealectomized and simultaneously pinealecyomized and thymectomized rats. Oncology. 1976; 33:3–8.
Savino W, Dardenne M. Neuroendocrine control of thymus physiology. Endocr Rev. 2000; 21:412–43.
Tian YM, Zhang GY, Dai YR. Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice. Immunol Lett. 2003; 88:101–4.
Vishwas DK, Haldar C. Photoperiodic induced melatonin regulates immunity and expression pattern of melatonin receptor MT1 in spleen and bone marrow mononuclear cells of male golden hamster. J Photochem Photobiol B. 2013c; 128:107–14.
Yao Q, Doan LX, Zhang R, Bharadwaj U, Li M, Chen C.Thymosin-alpha1 modulates dendritic cell differentiation and functional maturation from human peripheral blood CD14+ monocytes. Immunol Lett. 2007; 110(2):110–20.
Zatz MM, Godstein AL. Thymosins, lymphokines and the immunology of aging. Gerontology. 1985; 31:263–72.